Ralitrexed (Tomudex) or Nordic-FLv regimen in metastatic colorectal cancer: a randomized phase II study focusing on quality of life, patients' preferences and health economics.

Raltitrexed (Tomudex) is proven effective in metastatic colorectal cancer. Between 1998-2000, 25 patients were included in a randomized phase II study comparing raltitrexed (13 patients) and the Nordic FLv regimen (12 patients). 23 patients were evaluable for response. The overall response rate was 2/12 (1 CR, 1 PR) in the raltitrexed arm and 1/11 (1 CR) in the Nordic FLv arm, respectively. There was no difference in overall survival (raltitrexed--14.7 months, Nordic FLv--15.4 months). 23 patients were evaluable for Quality of Life (QoL) analysis. 23/25 and 17/21 questionnaires (EORTC QLQ C-30) were returned at baseline and first evaluation. Raltitrexed tended to be the most toxic regimen, when looking at nausea and vomiting, appetite loss, diarrhea and global QoL. However, most patients (65%) recommended the raltitrexed treatment schedule. The total treatment cost was equal in both arms (about 6,800 EURO/patient) and the hospital/hospital hotel stay costs accounted for more than half of it.

Blood transfusion and recurrence of colorectal cancer.

Because perioperative blood transfusions have been shown to have an impaired effect on survival in patients with colorectal cancer, we examined retrospectively the records of 882 patients who had undergone curative operations: 170 patients had distant metastases at the time of operation. Of the 499 patients with colonic cancer 332 (67%) had received perioperative blood transfusions. The corresponding figure for the 213 patients with rectal cancer was 190 (89%). Colonic tumors recurred in 45% of the patients who received blood transfusions and in 39% of those who did not. Corresponding figures for tumors in the rectum were 54% and 55%. When dividing the patients with colonic cancer into different subgroups according to Dukes' grade we found differences in survival rates. The poorer survival for transfused patients was, however, only significant for those with Dukes' A tumors (p less than 0.05). This difference disappeared when the influence of age was eliminated. The estimated risk ratio of recurrence and death was 1.23 with the 95% confidence interval (0.99, 1.53) when taking Dukes' grade, current age and localization into account. Blood transfusion should be avoided if possible until adequate prospective studies have been carried out.

Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group.

A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.

Recurrent ulcer after treatment with cimetidine or sucralfate.

The recurrence of peptic ulcer disease after successful treatment with 400 mg cimetidine twice daily or 1 g sucralfate four times daily was investigated in a double-blind, 1-year follow-up study. Endoscopy was performed if ulcer symptoms recurred and 2-4 and 9-11 months after endoscopically confirmed healing of the initial ulcer. No anti-ulcer medication was permitted during the follow-up period. The recurrence rates were 71% in the cimetidine group (n = 143) and 68% in the sucralfate group (n = 115) (p greater than 0.3). The rate of asymptomatic ulcer relapse was 26% in the cimetidine and 23% in the sucralfate group (p greater than 0.4). The time to relapse did not differ between the treatment groups (p greater than 0.3). In the cimetidine group smokers had a higher 12-month recurrence rate than non-smokers, 83% compared with 58% (p less than 0.01). The corresponding figures in the sucralfate group were 76% and 57% (p = 0.057). The median time to recurrence in the cimetidine-treated group was 17 weeks among smokers, compared to 43 weeks among non-smokers (p less than 0.001). In the sucralfate-treated group the median time to recurrence was 23 weeks among smokers and 32 weeks among non-smokers (p greater than 0.3). Pre-study use of non-steroidal anti-inflammatory drugs and the time to healing of the initial ulcer did not influence the relapse rates in either of the treatment groups.

Short-term treatment of prepyloric ulcer. Comparison of sucralfate and cimetidine.

A double-blind, randomized, multicenter study was performed to compare the effect of sucralfate (1 g qid) and cimetidine (400 mg bid) in the treatment of prepyloric ulcer. Altogether 142 patients (68 in the sucralfate and 74 in the cimetidine group) with endoscopically confirmed ulcer within 2 cm of the pylorus completed the study. Endoscopic follow up was performed after four weeks and, if the ulcer was not healed, after eight weeks of treatment. After four weeks, 65% of the ulcers in the sucralfate group were healed, compared to 70% in the cimetidine group. There was no significant difference between sucralfate and cimetidine at either time point. The 95% confidence interval for the difference in ulcer healing with sucralfate or cimetidine ranged from +4 to -19% at eight weeks. Said another way, with an observed difference of 7% (83% vs 90%), the 95% confidence limit ranged from 4% in favor of sucralfate to 19% in favor of cimetidine. Symptomatic relief, antacid intake, and side effects did not differ significantly between the two groups. The healing rate of prepyloric ulcer in this study is similar to that reported for duodenal ulcer after four and eight weeks when treated with sucralfate or cimetidine. Sucralfate is safe and as effective as cimetidine in the short-term treatment of prepyloric ulcer.

Treatment of acute duodenal ulcer--a Swedish multicenter study.

Medical ulcer therapy focuses on enhancing mucosal defence mechanisms or reducing intraluminal acidity. In this Swedish multicenter, randomized double-blind study these two principles were compared in the treatment of acute duodenal ulcerations. Sucralfate (Andapsin 1g X 4) or cimetidine (Tagamet 400mg X 2), together with antacid tablets (Novalucol), were supplied to patients with acute ulcerations in the pyloric ring or duodenal bulb. Endoscopy was performed at inclusion, after four weeks and in some patients also after eight weeks. Besides healing rate, symptoms and antacid intake, smoking and side effects were recorded on a special protocol. 371 patients from 15 centers completed the trial. At inclusion the patient groups did not differ in any essential aspect. At four weeks 71% of 177 patients on sucralfate and 77% of 194 on cimetidine were healed. The corresponding figures for eight weeks were 86% (suc) and 92% (cim). The difference is not significant, the 95% confidence interval for the difference in ulcer healing efficacy of sucralfate compared with cimetidine at eight weeks was -12% to +5%. Antacid intake and symptoms decreased rapidly and equally in both groups. Side effects related to the treatments were uncommon. It is concluded that sucralfate and cimetidine, representing two different principles in medical ulcer treatment, are both very effective and compare well in the short term treatment of acute duodenal ulcer.

Swedish multicenter study on prepyloric and gastric ulcer.

A double-blind, randomized, multicenter study was performed to compare the effects of sucralfate and cimetidine for the short-term treatment of gastric and prepyloric ulcers. Ulcer healing was evaluated endoscopically at 4-week intervals up to 8 weeks in the PPU study and up to 12 weeks in the GU study. A total of 142 PPU and 134 GU patients completed the study. The overall healing rates after 8 weeks in the PPU study were 83% for the sucralfate group and 90% for the cimetidine group (NS), while the cumulative healing rates after 12 weeks in the GU study were 98% for the sucralfate group and 94% for the cimetidine group (NS). The confidence interval means that the 95% confidence limit ranges from 11% in favour of sucralfate to 2% in favour of cimetidine in the GU study and corresponding figures of 4% 19% in the PPU study. There were significantly more patients in the cimetidine group taking antacid tablets after 3 weeks in the GU study. Symptomatic relief did not differ significantly. Reported side effects and symptoms, pooled together with our duodenal ulcer study, were mostly non-specific and in some part related to the ulcer disease. In conclusion, sucralfate and cimetidine are both excellent healing agents for the short-term treatment of PPU and GU. Both give rapid and good symptomatic relief with no side effects of any importance.

Pyoderma gangrenosum after colectomy for inflammatory bowel disease. Case report.

Pyoderma gangrenosum appeared parastomally after proctocolectomy and ileostomy for ulcerative colitis in two patients. The cases are described and diagnosis and treatment are discussed.

Treatment of peptic ulcers--acid reduction or cytoprotection?

In a Swedish multicenter double blind trial cimetidine was compared to sucralfate in the treatment of peptic ulcer. Patients with endoscopically verified gastric, prepyloric and duodenal ulcers were treated with cimetidine 400 mg x 2 or sucralfate 1 g x 4 for four to eight weeks. Gastric ulcers were treated up to 12 weeks. Patients with healed ulcers were followed for up to 12 months. During follow-up without any anti ulcer treatment control endoscopy was performed 2-4 and 9-11 months after endoscopic healing and at symptomatic recurrence. 647 patients were studied (334 cimetidine and 313 sucralfate). 258 patients were included in the 12 months' follow up: of these 143 were previously treated with cimetidine and 115 with sucralfate. Healing rates were 92% in patients treated with cimetidine and 87% in those given sucralfate (ns). Symptomatic relief and ulcer recurrence did not differ between the treatments. Smoking significantly increased recurrence rate and shortened the time to recurrence in the cimetidine treated patients, but not in the sucralfate group. Cimetidine and sucralfate compared well in all aspects of acute peptic ulcer treatment and recurrence during one year of follow up.

Ulcer recurrences following initial ulcer healing with sucralfate or cimetidine.

Ulcer relapses after short-term treatment of duodenal, prepyloric and gastric ulcers with Cimetidine 400 mg b.d. or Sucralfate 1 g q.i.d. were studied in 270 patients over one year. Endoscopic examinations were carried out 2-4 and 9-11 months after ulcer healing or when symptoms occurred. Ulcer relapses were found in 59% of the Cimetidine-treated patients and 51% of those treated with Sucralfate, and a further 21% and 16% respectively had endoscopically verified erosive gastroduodenitis. The cumulative recurrence rate in smokers was 82% and that in non-smokers 51% (p less than 0.001). Relapses among the Cimetidine patients occurred more often in those who smoked or had irregular working hours. The onset of the relapse was not related ulcer healing time. The ulcer relapses appeared in the same region as the initial ulcer in 88% of cases and exactly at the original site in 33%. These results suggest that cytoprotection by Sucralfate did not result in fewer or later relapses than acid reduction by Cimetidine. Cigarette smoking obviously increases the risk of relapse in patients with healed peptic ulcers.

Selective cefuroxime prophylaxis following colorectal surgery based on intra-operative dipslide culture.

The concept of a very limited effective period for prophylactic antibiotic action was challenged in a prospective, controlled and randomized study featuring a simplified method for assessing the degree of contamination in the operative field during colorectal surgery. The 226 patients were given 1 g metronidazole IV on induction of anaesthesia and 12 h postoperatively. Following standardized saline irrigation of the abdominal cavity, a uriculture dipslide was dipped in the residual fluid just before abdominal closure. The dipslide was incubated for 18 h, and colony counts of coliforms and Staphylococcus aureus were made. The number of colony-forming units (CFU) was classified as 0, 1-4 or greater than or equal to 5 (n = 123, 33 and 70). The patients with CFU greater than or equal to 5 were randomized to receive cefuroxime (1.5 g IV/8 h for 2 days) or no more antibiotics. In the patients given only metronidazole, the incidence of postoperative infections rose with the colony counts (5.7, 9.1 and 41.2 per cent with CFU 0, 1-4 and greater than or equal to 5). Addition of cefuroxime reduced the 41.2 per cent infection rate to 8.3 per cent (P = 0.003). The method thus identified a high-risk group in which a short postoperative course of cefuroxime significantly lowered the rate of sepsis.

Short term treatment of gastric ulcer: a comparison of sucralfate and cimetidine.

A double blind randomised study was undertaken to compare sucralfate and cimetidine in short term treatment of gastric ulcer. The study included 149 patients with endoscopically confirmed gastric ulcerations. Patients with prepyloric ulcers 2 cm or less from the pyloric ring were not accepted for participation in the trial. Ulcer healing was assessed endoscopically at four week intervals. A total of 134 patients completed the study. The cumulative healing rates after 12 weeks were 98% for sucralfate and 94% for cimetidine treated patients. After four and eight weeks, the healing rates were 61% and 94% for sucralfate and 69% and 94% for the cimetidine-treated group respectively. No statistically significant differences in healing rates were seen. The 95% confidence interval was calculated for the difference between the ulcer healing rates of sucralfate and cimetidine. This interval was found to range between +11% and -2% after 12 weeks of treatment - that is, the healing efficacy of sucralfate was calculated to be at most 11% better or 2% worse than that of cimetidine. No significant differences in symptom relief, side effects or antacid intake were found.

Short-term treatment of duodenal ulcer. A comparison of sucralfate and cimetidine.

A multicenter randomized double-blind study was performed to compare a cytoprotective agent (sucralfate) and an acid-reducing agent (cimetidine) in the treatment of duodenal ulcer. Patients with acute ulcerations in the pyloric ring and duodenal bulb confirmed by endoscopy were included in the trial. All patients were examined after 4 and, if not cured, after 8 weeks. A total of 371 patients from 15 centers completed the trial. The patient groups were comparable. At 8 weeks 86% of 177 patients receiving sucralfate treatment were cured, compared with 92% of 194 receiving cimetidine (NS). The corresponding figures at 4 weeks were 71% (sucralfate) and 77% (cimetidine) (NS). The 95% confidence interval for the difference in ulcer healing efficacy of sucralfate compared with cimetidine at 8 weeks was -12% to +5%. Antacid intake and symptoms decreased rapidly in both groups. Three patients were withdrawn owing to side effects. It is concluded that sucralfate and cimetidine. representing two different approaches to ulcer therapy, are both very effective and compare well with regard to ulcer healing, symptom relief, and side effects in the short-term treatment of acute duodenal ulcer.

Colonic haemorrhage in diverticular disease--diagnosis and treatment.

A retrospective review of acute diverticular disease in 230 patients revealed that 46 had presented with haemorrhage. The symptoms, investigations and outcome in these 46 cases are reported and the optimum management of profuse colonic haemorrhage is discussed.