Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double-blind, controlled trial. A phase II study to evaluate WF10 in patients with late hemorrhagic radiation cystitis and proctitis. Short-chain fatty acids in the treatment of radiation proctitis: a randomized, double-blind, placebo-controlled, cross-over pilot trial. Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Metronidazole in the treatment of chronic radiation proctitis: clinical trial.
Short chain fatty acids are the main energy source of colonocytes and their use may be impaired in chronic radiation proctitis. The aim of the present study was to evaluate the therapeutic effect of short chain fatty acid enemas in patients with chronic radiation proctitis.
                A prospective, randomized, double-blind trial comparing short chain fatty acid enemas with placebo was conducted in 19 patients with chronic radiation proctitis. Short chain fatty acid enemas contained 60 mM sodium acetate, 30 mM sodium propionate, and 40 mM sodium butyrate. The treatment period lasted five weeks and patients were followed up for six months.
                On admission, both groups were similar regarding all parameters evaluated. After five weeks short chain fatty acid-treated patients showed a significant decrease in the number of days with rectal bleeding from the previous week (4.4+/-1.8 to 1.4+/-2.2; P = 0.001) and an improvement of endoscopic score (4.8+/-1.4 to 2.2+/-1.2; P = 0.001). Hemoglobin values were also significantly higher in short chain fatty acid-treated patients (13.1+/-0.9 g/dl vs. 10.7+/-2.1 g/dl; P = 0.02). Mucosal DNA and protein concentrations decreased in both groups but significantly so only in placebo-treated patients (P = 0.05). Changes in histologic parameters were not significant in either group. Although short chain fatty acid-treated patients did not get worse in the next six months, placebo-treated ones gradually improved, and at the end of six months, differences between the two groups were no longer observed.
                Short chain fatty acid enemas can accelerate the process of healing in chronic radiation proctitis, but treatment has to be continuous if a complete and sustained clinical, endoscopic, and histologic response is to be obtained. To evaluate efficacy and safety of WF10 (TCDO iv solution) therapy in patients with late hemorrhagic radiation cystitis and proctitis in a long-term follow up.
                From February 1999 to July 2001, 30 symptomatic patients with endoscopically confirmed grade 2 and 3 late hemorrhagic cystitis (n = 16) and proctitis (n = 14) were treated with WF10. The dose was 0.5 ml/kg BW, diluted in 250 ml 5%D/W, administered by intravenous infusion over 2 h, 5 consecutive days, every 3 weeks for 2-4 cycles, combined with standard therapy. The patients were clinically followed up every 3 weeks for 3 months, then every 3 months for 1 year and then every 3-6 months. The study endpoints were immediate response with improvement to Grade 0-1 within 3 months and the incidence of recurrence to Grade > or =2 during the follow up time.
                After completion of the WF10 therapy, 14 cystitis patients (88%) had improved to grade 0-1 hematuria, and 14 proctitis patients (100%) had improved in bleeding per rectum to grade 0-1 within 3 months. The median follow up time was 51 months. During the follow up period, among the responders, 4 cystitis patients (28%) had recurrent hematuria of grade 2 and two proctitis patients (14%) had recurrent bleeding per rectum of grade 2 and 3. No treatment toxicity was observed.
                The WF10 therapy combined with conventional treatment is simple and safe with long-term efficacy in the treatment of late hemorrhagic radiation cystitis and proctitis. Treatment of chronic radiation proctitis remains unsatisfactory. Short-chain fatty acids are the preferred energy source for the colonic epithelium. We aimed to determine for the first time whether topical butyric acid enemas relieve symptoms and improve the macroscopic and microscopic findings in chronic radiation proctitis.
                A randomized, double-blind, placebo-controlled, cross-over pilot trial compared patients given two weeks of butyric acid enemas (40 mmol) twice per day with those given placebo, with a one-week washout period; 15 patients were randomized and 12 completed both arms of the trial. A total symptom score combined six symptom items per week (rectal pain, episodes of rectal bleeding, amount of blood passed, days with diarrhea, number of stools, and urgency). Symptom, endoscopic, and histologic scores were obtained at the beginning of the study and again at the last week of each treatment arm.
                Total symptom score at baseline (median, 5.5) improved for those patients receiving active treatment (median, 3.5), but compared with placebo (median, 4.5), the change was not significant. Endoscopic appearances were largely unaltered by active treatment. Histology was abnormal in 82 percent of patients receiving placebo compared with 55 percent of those given butyric acid enemas (P = not significant).
                Butyric acid enemas do not appear to be superior to placebo in the treatment of chronic radiation proctitis. In a prospective study, 37 consecutive patients with radiation-induced proctosigmoiditis were randomized to receive a four-week course of either 3.0 g oral sulfasalazine plus 20 mg twice daily rectal prednisolone enemas (group I, N = 18) or 2.0 g twice daily rectal sucralfate enemas plus oral placebo (group II, N = 19). The two groups were comparable with respect to demographic features, duration of symptoms, and clinical and endoscopic staging of the disease. Fifteen patients in group I and 17 in group II completed the trial. At four weeks, both groups showed significant clinical improvement (P less than 0.01 for group I and P less than 0.001 for group II) and endoscopic healing (P less than 0.01 for group I and P less than 0.001 for group II). When the two groups were compared, sucralfate enemas showed a significantly better response as assessed clinically (P less than 0.05), although endoscopically the response was not statistically different (P greater than 0.05). We conclude that both treatment regimens are effective in the management of radiation proctitis. Sucralfate enemas give a better clinical response, are tolerated better, and because of the lower cost should be the preferred mode of short-term treatment. To evaluate the effectiveness of metronidazole in combination with corticosteroids in enema and mesalazine (5-aminosalicylic acid) in comparison with the same protocol without metronidazole in the treatment of chronic radiation proctitis.
                Sixty patients with rectal bleeding and diarrhea were randomly divided into two groups. Patients in the first group were treated with metronidazole (3x400 mg orally per day), mesalazine (3x1 g orally per day), and betamethasone enema (once a day during 4 weeks). Patients in the second group were treated with mesalazine and betamethasone enema, but without metronidazole. The efficacy of metronidazole was assessed on the basis of rectal bleeding, diarrhea, and rectosigmoidoscopy findings in all patients.
                The incidence of rectal bleeding and mucosal ulcers was significantly lower in the metronidazole group, 4 weeks (p=0.009), 3 months (p=0.031), and 12 months (p=0.029) after therapy. There was also a significant decrease in diarrhea and edema in the metronidazole group, 4 weeks (p=0.044), 3 months (p=0.045), and 12 months (p=0.034) after treatment.
                Metronidazole in combination with mesalazine and betamethasone enemas successfully treats rectal bleeding and diarrhea in chronic radiation proctitis.
Late radiation complications are relatively rare, involving potential carers and poor diagnostic criteria. Although certain interventions look promising (e.g. rectal sucralfate, adding metronidazole to the anti-inflammatory regime and heater probes), single small studies, even if well conducted provide insufficient evidence. The episodic and variable nature of late radiation proctitis requires large multi-centre placebo-RCTs to establish whether particular treatments are effective. 
Regional or centralised registers of radiation toxicity should be established so interventions can be administered in the setting of multi-centre RCTs with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data including quality of life (QOL) evaluations.