Rectal Bleeding and Its Management after Irradiation for Cervix Cancer / 대한방사선종양학회지

PURPOSE: Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. MATERIALS AND METHODS: A total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The point A dose from the HDR brachytherapy was 28 Gy to 30 Gy (4 Gyx7, or 5 Gyx6). The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months (12~86 months). RESULTS: The incidence of rectal bleeding was 12.7% (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was 8.5%. Most complications (92.6%) developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding : an icruCRBED greater than 100 Gy (19.7% vs. 4.2%), an EBRT dose to the parametrium over 55 Gy (22.1% vs. 5.1%) and higher stages of III and IV (31.8% vs. 10.5%). In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was performed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. CONCLUSION: Moderate and severe rectal bleeding occurred in 8.5% of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.

Radiation-Induced Proctitis in Rat and Role of Nitric Oxide / 대한방사선종양학회지

PURPOSE: Proctitis is one of acute complications encountered when radiotherapy was applied to the pelvis. Radiation-induced proctitis represents similar microscopic findings that are observed in inflammatory bowel disease (IBD). Nitric oxide (NO) plays an important role in the inflammatory process and many data suggest a close relationship between NO production and gastrointestinal inflammation. This study was aimed to establish the optimal radiation dose for radiation-induced proctitis in rat and to find a relationship between radiation proctitis and NO production. MATERIALS AND METHODS: Female Wistar rats, weighing from 150 to 220 g, received various doses(10-30 Gy) of radiation to the rectum. On the 5th and 10th day after irradiation, rectal specimens were evaluated grossly and microscopically. In addition, the degree of NO production by irradiation dose was evaluated by study with NOS expression and nitrite production in the irradiated rectal tissue. To evaluate relationship between radiation proctitis and NO, we administered aminoguanidine, iNOS inhibitor and L-arginine, substrate of NOS to rats from 2 days before to 7 days after the irradiation. RESULTS: There were obvious gross and histological changes after 17.5 Gy or higher radiation dose but not with 15 Gy or less radiation dose. Twenty Gy or higher dose of radiation caused Grade 4 damage in most of rectal specimens which were more likely to be related to the late complications such as fibrosis, rectal bleeding and rectal obstruction. A single fraction of 17.5 Gy to the rat rectum is considered to be an optimal dose to produce commonly experienced proctitis in the clinic. The result demonstrated that severity of microscopic damage of rectal mucosa from irradiation significantly correlated with iNOS overexpression. However, administration of iNOS inhibitor or substrate of iNOS did not influence the degree of rectal damage. CONCLUSION: A single fraction of 17.5 Gy irradiation to the rat rectum considered to be an optimal dose for radiation induced proctitis model. These results indicated that an excess production of NO contributes to pathogenesis of radiation-induced proctitis in part but was not the direct cause of rectal damage.

Radiation Effect on NO, NOS and TGF-beta Expressions In Rat Lung / 대한방사선종양학회지

PURPOSE: NOS2 induce NO production and NO activate TGF-beta. The TGF-beta is a inhibitor of NOS2. If this negative feedback mechanism operating in radiation pneumonitis model, NOS2 inhibitor may play a role in TGF-beta suppression. We planned this study to evaluate the expression patterns of NO, NOS2 and TGF-beta in vivo radiation pneumonitis model. MATERIALS AND METHODS: Sixty sprague-Dawley rat were irradiated 5 Gy or 20 Gy. They were sacrificed 3, 7, 14, 28 and 56 days after irradiation. During sacrifice, we performed broncho-alveolar lavage (BAL). The BAL fluids were centrifuged and supernatents were used for measure NO and TGF-beta, and the cells were used for RT-PCR. RESULTS: After 5 Gy of radiation, NO in BAL fluid increased at 28 days in both lung and TGF-beta in left lung at 56 days. NO increased in BAL fluid at 28 days in both lung after irradiation and TGF-beta in right lung at 28-56 days after 20 Gy of radiation. After 5 Gy of radiation, NOS2 expression was increased in right lung at 14 days, in both lung at 28 days and in left lung at 56 days. TGF-beta expression was reduced in both lung at 28 days and increased in left lung at 56 days. CONCLUSIONS: The proposed feedback mechanism of NO, NOS2 and TGF-beta was operated in vivo radiation pneumonitis model. At 56 days, however, NOS2 and TGF-beta expressed concurrently in left lung after 5 Gy and in both lung after 20 Gy of radiation.