skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT)

Abstract

The purpose of the study is to obtain dose guidelines for the delivery of intraoperative radiotherapy to the liver of patients with colorectal liver metastases. Following partial resection of the liver, a single high dose of 10, 20, 25, and 30 Gy intraoperative radiotherapy was applied to both the resection plane as well as a nonsurgically manipulated part of the liver of 25 beagles. The temporal sequence of histological and ultrastructural changes of these irradiated parts of the liver tissue was investigated. The feasibility of delivering a single large dose of intraoperative electron beam radiotherapy to the normal and partially hepatectomized liver was experimentally investigated in a canine study. There were no postoperative complications, no morbidity or mortality with a minimal follow-up of 1 year. Autopsy performed 3 months following irradiation showed only mild histopathological changes. One year following intraoperative radiotherapy more distinct histopathological changes consisting of capsular thickening, diffuse parenchymal fibrosis and subcapsular hepatocellular atrophy were found. The liver function remained intact. This study demonstrated that intraoperative radiotherapy to part of the liver in the canine model can be safely applied and doses up to 30 Gy are well tolerated. 34 refs., 6 figs., 1 tab.

Authors:
; ; ; ;  [1];  [2]
  1. (Univ. Hospital, Groningen (Netherlands))
  2. (Groningen State Univ. (Netherlands))
Publication Date:
OSTI Identifier:
6568813
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States); Journal Volume: 27:5
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; LIVER; BIOLOGICAL RADIATION EFFECTS; SURGERY; RADIOTHERAPY; SIDE EFFECTS; BIOLOGICAL MODELS; BIOLOGICAL EFFECTS; BODY; DIGESTIVE SYSTEM; GLANDS; MEDICINE; NUCLEAR MEDICINE; ORGANS; RADIATION EFFECTS; RADIOLOGY; THERAPY; 560152* - Radiation Effects on Animals- Animals

Citation Formats

Chromheecke, M., Oldhoff, J., Hoekstra, H.J., Vermeij, J., Grond, A.J.K., and Konings, A.W.T. Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT). United States: N. p., 1993. Web. doi:10.1016/0360-3016(93)90535-4.
Chromheecke, M., Oldhoff, J., Hoekstra, H.J., Vermeij, J., Grond, A.J.K., & Konings, A.W.T. Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT). United States. doi:10.1016/0360-3016(93)90535-4.
Chromheecke, M., Oldhoff, J., Hoekstra, H.J., Vermeij, J., Grond, A.J.K., and Konings, A.W.T. 1993. "Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT)". United States. doi:10.1016/0360-3016(93)90535-4.
@article{osti_6568813,
title = {Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT)},
author = {Chromheecke, M. and Oldhoff, J. and Hoekstra, H.J. and Vermeij, J. and Grond, A.J.K. and Konings, A.W.T.},
abstractNote = {The purpose of the study is to obtain dose guidelines for the delivery of intraoperative radiotherapy to the liver of patients with colorectal liver metastases. Following partial resection of the liver, a single high dose of 10, 20, 25, and 30 Gy intraoperative radiotherapy was applied to both the resection plane as well as a nonsurgically manipulated part of the liver of 25 beagles. The temporal sequence of histological and ultrastructural changes of these irradiated parts of the liver tissue was investigated. The feasibility of delivering a single large dose of intraoperative electron beam radiotherapy to the normal and partially hepatectomized liver was experimentally investigated in a canine study. There were no postoperative complications, no morbidity or mortality with a minimal follow-up of 1 year. Autopsy performed 3 months following irradiation showed only mild histopathological changes. One year following intraoperative radiotherapy more distinct histopathological changes consisting of capsular thickening, diffuse parenchymal fibrosis and subcapsular hepatocellular atrophy were found. The liver function remained intact. This study demonstrated that intraoperative radiotherapy to part of the liver in the canine model can be safely applied and doses up to 30 Gy are well tolerated. 34 refs., 6 figs., 1 tab.},
doi = {10.1016/0360-3016(93)90535-4},
journal = {International Journal of Radiation Oncology, Biology and Physics; (United States)},
number = ,
volume = 27:5,
place = {United States},
year = 1993,
month =
}
  • An experimental study of bladder tolerance to intraoperative radiotherapy (IORT) was designed using a large animal model (adult American Foxhounds, weight 25-30 kg) to access acute and late radiation effects. Dogs were subjected to laparotomy where the bladder was mobilized and IORT was delivered using a 5 cm circular cone through a cystotomy incision with 12 MeV electrons. The bladder trigone including both ureteral orifices and the proximal urethra was irradiated in groups of 3 dogs with doses of 0, 20, 25, 30, 35, and 40 Gy. Dogs were followed clinically with repeat urinalysis, intravenous pyelogram (IVP), and cystometrogram atmore » 1 month and then Q6 months for up to 4 years. One dog from each dose group was sacrificed electively at 1 and 2 years, whereas the other dog is being followed clinically for a minimum of 4 years. Complete autopsies were performed with particular attention to genitourinary and pelvic structures. No clinically detectable acute toxicity resulted from IORT to the bladder. Three of 15 IORT dogs (1 each at 25, 35, and 40 Gy) showed obstruction of a ureteral orifice with 2 dogs dying of renal failure secondary to bilateral hydronephrosis within 1-2 years of treatment. The remaining 12 IORT dogs and 3 control dogs have normal repeat IVP's and renal function with up to 4 years of follow-up. Serial cystometry demonstrates no major loss of bladder contractility or volume. At autopsy, histological changes of mucosal thinning and telangiectasia with submucosal fibrosis were confined to the IORT field and appeared dose-related. However, the bladder epithelium remained intact at all doses. The ureterovesical junction in animals receiving 20 Gy showed mild fibrosis of the lamina propria and moderate chronic inflammation. Above 20 Gy, these histological changes at the U-V junction were more pronounced with gross stenosis in 3 animals as predicted by the IVP.« less
  • Acute and chronic histopathologic and biochemical effects on normal canine liver tissue from a single intraoperative application of heat and radiation, heat alone, and radiation alone have been evaluated in 54 adult mongrel dogs. The tolerance of normal canine liver tissue to single doses of intraoperative radiation therapy (IORT) was evaluated at doses of 5, 10, 20, 30, and 40 Gy. In addition, intraoperative interstitial hyperthermia (43{degree}C, 60 minutes, 500 kHz) was applied alone and in combination with a single intraoperative dose of 30 Gy from an 18 MeV electron beam. Blood flow at the center of the implantation sitemore » before, during and after hyperthermia treatments was also evaluated.« less
  • We studied the feasibility of delivering a large single dose of intraoperative radiation as an adjuvant to partial hepatic resection. Intraoperative radiation therapy (IORT) was delivered to the remaining liver of 84 rats after partial hepatectomy to determine the acute and chronic effects of treatment on blood chemistry values, histology, survival, hepatic regeneration, and cellular appearance of the normal liver. Transient elevations in SGOT, SGPT, and alkaline phosphatase were attributed both to hepatectomy and to liver parenchymal damage induced by IORT. Microscopic examination upon necropsy, performed at frequent intervals post-treatment revealed hepatic capsular thickening with some alteration of liver architecturemore » mainly underneath the capsule, with localized inflammation and some areas of necrosis. Survival in all groups was 100% at 45 days. Liver weight increase proved to be dose-dependent and displayed a bisphasic pattern. This study demonstrated that IORT is a feasible adjunct to surgical resection of the liver in the rat model.« less
  • IORT may be a potentially useful adjunctive treatment combined with surgery and/or external beam irradiation in treating locally advanced lung and esophageal tumors. To begin investigation of this modality, the tolerance of intact mediastinal structures to IORT was studied using adult American Foxhounds (wt. 25-30 kg). Groups of six animals received IORT to doses of 20, 30, or 40 Gy to two separate intrathoracic ports, using 9 MeV electrons to treat a portion of the collapsed right upper lobe, and 12 MeV electrons to treat the mediastinal structures. A group of three dogs received thoracotomy with sham irradiation. Two dogsmore » from each treatment dose group, as well as one sham-irradiated control, were sacrificed electively at 1, 3, and 12 months following IORT. There were no acute nor late IORT related mortalities. Post-operative weight loss was minimal (average 4.5% of pre-operative weight) for all dogs. Serial esophagrams showed no inflammation or ulceration. No cardiac nor pulmonary changes were noted clinically. At autopsy, the irradiated lung showed evidence of acute pneumonitis at 1 month with progressive fibrosis at 3 months and 1 year. Esophageal reactions were minimal, with only two dogs (one 30 Gy and one 40 Gy) demonstrating histologically confirmed esophagitis at 1 month. Tracheal changes were minimal. Cardiac damage was evident in the right atrial tissues. In several dogs, this cardiac damage ranged from myocardial vascular changes to frank ischemic necrosis noted at 1 and 3 months, and dense fibrosis at 1 year. The phrenic nerves showed normal function, but had evidence of perineural fibrosis. The large vessels demonstrated only mild histologic evidence of irradiation. The results of this large animal study suggest that intact mediastinal structures will tolerate small volume IORT to doses of 20 Gy without significant clinical sequellae. (Abstract Truncated)« less
  • The purpose of this study was to check the setup and dose delivered to the patients during intraoperative electron beam radiation therapy (IORT) for prostate cancer. Twenty eight patients underwent IORT after radical prostatectomy for prostate cancer by means of a dedicated mobile accelerator, Novac7 (by Hitesys, SpA, Italy). A 9 MeV electron beam at high dose per pulse was used. Eighteen patients received IORT at escalating doses of 16, 18, and 20 Gy at 85% isodose, six patients for each dose level. Further, ten patients received 20 Gy at 85% isodose. The electron applicator position was checked in allmore » cases by means of two orthogonal images obtained with brilliance intensifier. Target and organ at risk doses were measured in vivo by a MOSFETs dosimetry system. MOSFETs and microMOSFET dosimeters were inserted into sterile catheters and directly positioned into the rectal lumen, for ten patients, and into the bladder to urethra anastomosis, in the last 14 cases. Verification at 0 deg. led to very few adjustments of setup while verifications at 90 deg. often suggested to bring the applicator closer to the target. In vivo dosimetry showed an absorbed dose into the rectum wall {<=}1% of the total dose. The average dose value inside the anastomosis, for the 12 patients analyzed, was 23.7 Gy with a standard deviation of {+-}7.6%, when the prescription was 20 Gy at 85% isodose. Using a C-arm mobile image intensifier, it is possible to assess if the positioning is correct and safe. Radio-opaque clips and liquid were necessary to obtain good visible images. In vivo MOSFETs dosimetry is feasible and reliable. A satisfactory agreement between measured and expected doses was found.« less