Randomized trial of pentoxifylline and vitamin E vs standard follow-up after breast irradiation to prevent breast fibrosis, evaluated by tissue compliance meter.

PURPOSE: To conduct a randomized clinical trial to determine whether the combination of pentoxifylline (PTX) and vitamin E given for 6 months after breast/chest wall irradiation effectively prevents radiation-induced fibrosis (RIF). METHODS AND MATERIALS: Fifty-three breast cancer patients with localized disease were enrolled and randomized to treatment with oral PTX 400 mg 3 times daily and oral vitamin E 400 IU daily for 6 months after radiation (n=26), or standard follow up (n=27). Tissue compliance meter (TCM) measurements were obtained at 18 months to compare tissue compliance in the irradiated and untreated breast/chest wall in treated subjects and controls. Measurements were obtained at 2 mirror image sites on each breast/chest wall, and the average difference in tissue compliance was scored. Differences in TCM measurements were compared using a t test. Subjects were followed a minimum of 2 years for local recurrence, disease-free survival, and overall survival. RESULTS: The mean difference in TCM measurements in the 2 groups was 0.88 mm, median of 1.00 mm (treated) and 2.10 mm, median of 2.4 mm (untreated). The difference between the 2 groups was significant (P=.0478). Overall survival (100% treated, 90.6% controls at 5 years) and disease-free survival (96.2% treated, 86.8% controls at 5 years) were not significantly different in the 2 groups. CONCLUSIONS: This study of postirradiation breast cancer patients treated with PTX/vitamin E or standard follow-up indicated a significant difference in radiation-induced fibrosis as measured by TCM. There was no observed impact on local control or survival within the first 2 years of follow-up. The treatment was safe and well tolerated. Pentoxifylline/vitamin E may be clinically useful in preventing fibrosis after radiation in high-risk patients.

Disturbed colonic motility contributes to anorectal symptoms and dysfunction after radiotherapy for carcinoma of the prostate.

PURPOSE: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. PATIENTS AND METHODS: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. RESULTS: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgency of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. CONCLUSION: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.

Temperature-controlled radiofrequency energy (SECCA) to the anal canal for the treatment of faecal incontinence offers moderate improvement.

BACKGROUND AND AIM: Faecal incontinence is a devastating complaint. Even after conservative treatment, many patients still remain incontinent. Few patients have a sphincter defect suitable for repair. Other emerging surgical therapies like dynamic gracilis plasty, neuromodulation or artificial bowel sphincter, carry side effects and show only moderate improvement. Temperature-controlled radiofrequency energy (SECCA) has shown promising results in the USA. Local tightening seems to be the mode of action with possible increased rectal sensitivity. We investigated the effectiveness of radiofrequency and possible changes in the anal sphincter with 3D-ultrasound in patients with faecal incontinence. PATIENTS AND METHODS: Eleven women, mean age 61 years (49-73) with long-standing faecal incontinence were included. Patients with large sphincter defects and anal stenosis were excluded. The SECCA procedure was performed under conscious sedation and local anaesthesia. Oral antibiotics were given. In four quadrants on four or five levels (depending upon length of the anus) radiofrequency was delivered with multiple needle electrodes. Patients were evaluated at 0, 6 weeks, 3 and 6 months and 1 year. Three-dimensional anal ultrasound was performed at 0 (before and after the procedure), 6 weeks and 3 months. Anal manometry and rectal compliance measurement were performed at 0 and 3 months. RESULTS: At 3 months, six of 11 patients improved, which persisted during follow-up of 1 year. The Vaizey score changed from 18.8 to 15.0 (P=0.03) and in those improved from 18.3 to 11.5 (P=0.03). Anal manometry and rectal compliance showed no significant changes, there was a tendency to increased rectal sensitivity concerning urge and maximal tolerated volume (both P=0.3). Responders compared with nonresponders showed no difference in test results. Side effects were local haematoma (2), bleeding 3 days (1), pain persisting 1-3 weeks (4) and laxatives-related diarrhoea during 1-3 weeks (4). CONCLUSION: The SECCA procedure seems to be promising for patients with faecal incontinence with a persisting effect after 1 year. No significant changes in tests were found.

The effects of local X-irradiation on the distensibility of the rectum in rats.

Proctometry was performed on female Wistar rats following irradiation of the rectum with single doses of 15, 18 and 22 Gy of X-rays. The results indicated a progressive increase in distensibility until week 29 after irradiation which was attributed to degenerative changes in the intestinal wall. A major factor which determines colorectal pressure is the neuromuscular activity, however, neuromuscular transmission was not affected by irradiation.

Determination of X-ray-induced damage to the murine colon using tissue compliance measurements.

A proctometroscope has been developed to measure the mechanical functioning of the colon in a murine model. A balloon-tipped probe is inserted into the colorectal region of anaesthetized mice and inflated hydraulically, at a constant rate, by a motor-driven syringe. Balloon pressure and volume are monitored, processed and plotted on a X-Y/t recorder. The balloon is inserted within the irradiated area, such that the centre of the balloon is 1 cm proximal to the anus, and inflated up to either a maximum volume of 100 microliters or a maximum pressure of 100 cmH2O, depending on which occurs first. Compliance (delta V/delta P) of the colon was measured at various intervals following X-irradiation, a dose-dependent decrease being observed at 24 weeks. This decrease was progressive with time out to 72 weeks postirradiation. The compliance measured, in both control and irradiated groups, was not dependent on the inflation rate used to make the determination, and no iatrogenic effects have been detected after repeated probing during a long-term study. The use of different anaesthetic agents was also investigated, no significant difference between the compliance of mice anaesthetized with the different agents being detected. Use of this technique provides fully quantitative data on the function of the colon following radiation injury, and provides an alternative to other physiological assays. The technique is non-destructive, rapid, easy to use and non-invasive to the tissue, thus the onset and progression of damage can be followed in each mouse over long postirradiation periods.