A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis.

Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated.

The outcome of surgery for colorectal cancer in the elderly: a 12-year review from the Trafford Database.

In this database study of 882 patients with colorectal cancer, elderly patients are of poor physical status on admission and are more likely to be either completely inoperable or require urgent surgery. The operative mortality rate is higher and hospital stay is likely to be longer. However, if the elderly patient is fit for surgery, survives for more than 30 days and a curative resection performed, the 5-year survival and post-operative complication rates are as good as those patients in the younger age groups.

Significant risk factors in elective colorectal surgery.

A prospective study of 618 patients undergoing elective colorectal surgery performed in a district general hospital over a 10-year period is reported. Multivariate analysis has been used in an attempt to identify risk factors. The risk of wound infection was increased if septicaemia, respiratory sepsis or faecal contamination was present, if the surgeon was a consultant and if increased risk of serious complications if the patient was male and of poor physical status. Operative mortality was significantly associated with poor physical status, respiratory sepsis and intra-abdominal abscess. Only three risk factors could be identified preoperatively: patient gender, physical status and seniority of surgeon. However, procedures low in the pelvis are more difficult and in this study group are also associated with a higher risk of wound infection. The majority of these procedures are performed by consultants. In addition, this study group has proportionally more female patients of poor physical status who are selectively being operated on by the consultant, seemingly indicating the 'consultant' as a risk factor.

Axillary sampling and radiotherapy does not compromise the patient with early breast cancer: Trafford database experience.

Local recurrence has been studied in a selected group of 379 patients, 39% of whom underwent simple mastectomy and 61% lumpectomy. The axilla was sampled in 52%, cleared in 8% and untreated in 40%. Axillary recurrence occurred in 16% of patients with a median follow-up of 54 months. Ninety-one per cent of these patients with lymph node recurrence had no surgery or sampling to the axilla, and a third received radiotherapy. Local recurrence was satisfactorily controlled by various modalities of treatment in all but 29 patients. Death related to distant metastasis in all but six of these 29 patients. Analysis suggests that patients with locally uncontrolled disease had aggressive tumours at diagnosis which were larger than average, most often grade 3 histologically and more frequently required mastectomy. Our results support previous studies indicating that survival would not be influenced by more radical surgery but that sampling followed by radiotherapy would have prevented the majority of our lymph node recurrences.

Stomach cancer--is it a lost cause?

A retrospective study of 7 years of endoscopy at Trafford General Hospital from 1986-1993 identified 143 patients diagnosed as having gastric cancer, of whom 13 cases were identified as early gastric cancer. Epigastric pain was the main symptom (66%) of those presenting with resectable disease. Weight loss (70%) was the most common symptom of patients presenting with advanced disease. Forty-seven patients had no surgery and 25 had palliative non-resective surgery. These two groups account for 50% of cases. With such a small detection rate of early gastric cancer and consequent curative surgery rate one must debate whether treatment of stomach cancer in the Trust hospital of the future is a lost cause.

Risk factors in patients presenting as an emergency with colorectal cancer.

Of 905 patients with colorectal cancer admitted to a single district general hospital, 272 (30 per cent) were admitted as emergencies. Emergency patients had more advanced tumours (Dukes stage B and C 96 per cent versus 88 per cent of those admitted electively, P < 0.006), a shorter history (median 3 versus 11 weeks, P < 0.0001), were less likely to be fully ambulatory (44 versus 80 per cent, P < 0.0001) and more likely to have abdominal pain (74 versus 51 per cent, P < 0.001) and vomiting (40 versus 10 per cent, P < 0.0001). More emergency patients were given stomas (56 versus 35 per cent, P < 0.0001) and died in hospital (19 versus 8 per cent, P < 0.0001). Of those who survived to be discharged, patients admitted as an emergency spent longer in hospital (median stay 16 versus 13 days, P < 0.0001) and had a poorer overall 5-year survival rate (29 versus 39 per cent, P = 0.0001). Emergency patients were significantly older (median 74 versus 72 years, P = 0.04) and much more likely to be widowed (41 versus 27 per cent, P = 0.0002) than those admitted for elective surgery. If the personal and resource disaster of emergency colorectal cancer admission is to be reduced, screening strategies targeted by demographic characteristics require investigation.

Physical status is the principal determinant of outcome after emergency admission of patients with colorectal cancer.

A prospective study of 825 consecutive patients with colorectal cancer presenting to three general surgeons in a district general hospital over a 10-year period are reported. In all, 735 patients had an operation and are grouped according to whether their operation was within 24 h of admission (n = 63), more than 24 h after admission (n = 151), or elective (n = 521). Operative mortalities for these groups were 15.9%, 15.2% and 6.5%, respectively, significantly higher in both the emergency groups. Delayed surgery to allow complete resuscitation did not improve the operative mortality when compared with those patients having urgent surgery. Both groups of emergency patients, delayed (27%) urgent (19%), showed poorer 5-year survival than the electively treated patients (36%), many dying of non-cancer causes. Patients who undergo emergency surgery for colorectal carcinoma are more likely to be in poorer physical condition than patients undergoing elective surgery for the same condition. It appears that the physical status is the principal determinant of outcome after emergency colorectal surgery rather than any other factor.

An evaluation of the effectiveness and safety of razoxane when used as an adjunct to surgery in colo-rectal cancer. Report of a controlled randomised study of 603 patients.

A prospective controlled randomised trial to evaluate the effectiveness and safety of razoxane is reported. Some 603 patients with colo-rectal cancer having curative surgery entered the study, and all have been followed up for a minimum of five years. Statistical analysis showed that razoxane treatment had no effect either beneficial or adverse on the rates of recurrence or on five year survival of patients with colo-rectal cancer. It is possible that a more prolonged course of razoxane might have significantly influenced survival. The incidence of severe adverse reaction was low but it is of concern that one patient developed leukaemia. Should razoxane be considered for future use it is recommended that continuous low dose therapy be given for no longer than 12 months. No renal, hepatic, pulmonary or cardiac toxicity was noted.

Peri-operative heparin: a possible adjuvant to surgery in colo-rectal cancer?

Analysis of data from a randomised trial of adjuvant razoxane involving 603 patients with colo-rectal cancer having curative surgery is reported. The results show that razoxane was ineffective but peri-operative subcutaneous heparin treatment apparently conferred a statistically significant improvement in survival at 5 years, or equivalently a reduction in the risk of death. This beneficial effect is apparent in both razoxane treated and control patients and is not explained by demonstrable differences between heparin and non-heparin treated patients in the distribution of known prognostic factors. Adjustment for these factors slightly increased the apparent magnitude of the beneficial effect.

Blood transfusion does not have an adverse effect on survival after operation for colorectal cancer.

The effect of perioperative blood transfusion on cancer progression remains controversial because retrospective clinical studies have produced conflicting results. We have collected data prospectively on 379 patients undergoing curative surgery for colorectal adenocarcinoma and assessed the effect of variables, including blood transfusion, on survival. Univariate and multivariate survival analysis has been carried out. When the end-point for analysis used was death due to recurrent colorectal carcinoma and non-cancer deaths were censored, there was no difference in cancer-specific survival between transfused and non-transfused patients. Survival analysis was also carried out without censoring the non-cancer deaths and clearly demonstrated how the statistical analysis and data interpretation could be distorted by age-related non-cancer deaths. The incidence of recurrence of colorectal carcinoma was not greater in the transfused group than in the non-transfused group. We conclude that blood transfusion should not be withheld in colorectal surgery for fear of worsening the prognosis.

Colorectal surgeons in district general hospitals produce similar survival outcomes to their teaching hospital colleagues: review of 5-year survivals in Manchester.

A study of 578 patients treated for colorectal cancer in the North-west region comparing survival after surgery in teaching and non-teaching hospitals was performed. All patients had a minimum of 5 years follow-up. A greater proportion of elderly and emergency patients were treated in the non-teaching hospitals. The number of operative mortalities and 5-year survival figures for all causes of death and for colorectal deaths alone were similar in teaching and non-teaching hospital patients.

Razoxane for Crohn's colitis and non-specific proctitis.

Oral razoxane 125 mg daily brought active Crohn's disease into remission when used alone and mainly on an out-patient basis in all nine patients studied. Remissions took several months to achieve, but no relapses have occurred on treatment and no surgery has been necessary in any of the patients. In the two patients with active non-specific proctitis, oral razoxane 125 mg daily rapidly controlled the condition. Apart from mild bone marrow toxicity in one patient, no other acute toxicity has occurred and no long-term side-effects have been observed.

Blood transfusion: an overused resource in colorectal cancer surgery.

The use of blood transfusion was examined in 476 patients who underwent curative surgery for large bowel cancer. Of these patients, 128 were not transfused while 348 received a total of 1174 units of blood. A patient was considered over-transfused if the predischarge haemoglobin was more than 12 g/dl. Using this criteria and accepting that single unit transfusions should be avoided, transfusion could have been avoided in 30% of the patients and a total of 377 units were given unnecessarily. Major under-transfusion did not occur; no patient being discharged with a haemoglobin of less than 9 g/dl. This study shows that blood transfusion is overused and the reasons for its use rarely recorded. In view of the morbidity related to transfusion, it is suggested that surgeons and anaesthetists reappraise their transfusion policy and the first step in this must be to record the reason for transfusion.

Curative resection: the major determinant of survival in patients with large bowel cancer.

Data collected prospectively from 578 patients with colorectal cancer managed by 12 Manchester surgeons were analysed to evaluate the effects on survival of prognostic, clinical and pathological factors. Available preoperative and perioperative factors were included in a stepwise regression analysis and curative resection was found to be most strongly associated with patient survival. Other variables ranked according to their relative importance were performance status, weight loss and sex. The finding of the study supports the need to establish an early diagnosis if long-term survival results are to improve.

A comparison of two doses of nizatidine versus placebo in the treatment of reflux oesophagitis.

Three-hundred and twenty-five patients with endoscopically verified oesophagitis entered a double-blind, randomized multicentre study that compared 300 mg nizatidine b.d., 300 mg nocte and placebo. The 6- and 12-week treatment responses were studied. Healing was defined as complete epithelialization of all oesophageal lesions. The healing rates were 40% in the 300 mg nizatidine b.d. group, 30% in the 300 mg nocte group and 26% in the placebo group at 6 weeks. The corresponding figures after 12 weeks of treatment were 50%, 44% and 34%, respectively. The healing rates were significantly different (P less than 0.05) between the high-dose nizatidine group and placebo only, both at 6 and 12 weeks. Despite a trend at both 6 and 12 weeks in favour of 300 mg nizatidine nocte compared to placebo, this was not significantly different. The most important factor for the outcome, apart from the treatment group, was the pre-entry severity of oesophagitis. The differences observed between treatment groups in healing rates, symptomatic relief, and antacid consumption appear to result mainly from the patients with moderate and severe oesophagitis upon entry. Nizatidine (300 mg) b.d. appeared to be safe and effective in the treatment of reflux oesophagitis.

Single dose cefotaxime plus metronidazole versus three dose cefuroxime plus metronidazole as prophylaxis against wound infection in colorectal surgery: multicentre prospective randomised study.

OBJECTIVE: To establish whether a single preoperative dose of cefotaxime plus metronidazole was as effective as a standard three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery. DESIGN: Prospective randomised allocation to one of two prophylactic antibiotic regimens in a parallel group trial. Group sequential analyses of each 250 patients were performed. SETTING: 14 District general and teaching hospitals. PATIENTS: 1018 Adults having colorectal operations were randomised, of whom 943 were evaluated. Demographic features, conditions requiring surgery, and operative procedures were similar in the two groups. Most patients had surgery for carcinoma of the colon or rectum. INTERVENTIONS: Group 1 received cefotaxime 1 g intravenously plus metronidazole 500 mg intravenously preoperatively. Group 2 received cefuroxime 1.5 g intravenously plus metronidazole 500 mg intravenously preoperatively, followed by cefuroxime 750 mg intravenously plus metronidazole 500 mg intravenously eight hours and 16 hours postoperatively. MAIN OUTCOME MEASURES: Development of surgical wound infection (as evidenced by the presence of pus), death, or discharge from hospital. RESULTS: Wound condition was scored on a five point scale on alternate days until discharge or for up to 20 days postoperatively. Wound infection rates were: group 1, 32/453 (7.1%; 95% confidence interval 4.7% to 9.4%); group 2, 33/454 (7.3%; 95% confidence interval 4.9% to 9.6%). Death rates (group 1: 26/470 (5.5%); group 2: 31/471 (6.6%], the incidence of postoperative complications, the median duration of hospital stay (12 days), and antibiotic tolerance were all similar in the two groups. Pooled data from groups 1 and 2 showed that wound infections were more frequent when minor faecal contamination had occurred at operation and when the duration of operation exceeded 90 minutes (greater than 90 min 11.2% of cases; less than 90 min 4.8%) and were associated with an extended hospital stay. CONCLUSIONS: A single preoperative dose of cefotaxime plus metronidazole is an efficacious as a three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery and has practical advantages in eliminating the need for postoperative antibiotics.

Effectiveness of two therapeutic antibiotic regimens in the treatment of serious post-operative infections.

A small prospective trial was conducted to evaluate the effectiveness and safety of a single antibiotic regimen, Augmentin, compared with a combination regimen of cefuroxime and metronidazole in the treatment of serious post-operative sepsis. Both regimens used were effective against Bacteroides and other anaerobes, with a similar satisfactory cure rate and no serious side effects. Intravenous Augmentin was easy to use and the change to oral therapy was significantly quicker than in the cefuroxime-metronidazole treatment arm. No significant resistance or serious adverse reaction was noted. The majority of patients had more than one site of infection, making selective antibiotic treatment difficult.

Comparison of two prophylactic single-dose intravenous antibiotic regimes in the treatment of patients undergoing elective colorectal surgery in a district general hospital.

Two hundred and twenty-nine patients were entered into a study to compare the effectiveness and safety of two single-shot antibiotic regimes in patients undergoing elective colorectal surgery in two district general hospitals. A single shot of intravenous (IV) latamoxef disodium was as effective as an IV combination of cefuroxime and metronidazole in control of wound infection following elective large bowel surgery when given as a bolus at the time of anaesthetic induction. The incidence of major wound infection was 6% and was evenly distributed in the two treatment groups. Half the major wound infections were associated with faecal fistulae. A single shot of IV antibiotic at the time of anaesthetic induction was safe, simple and an effective prophylaxis against major wound infection. There was a low incidence (1.3%) of serious postoperative bleeding and no serious adverse reactions were noted. The overall mortality was 9%. Death was significantly related to elderly patients, a poor performance status, operative contamination and wound infections.

Early diagnosis in colorectal cancer. Still no benefit?

Time to diagnosis from first symptoms has been assessed in 332 patients with colorectal cancer treated by the three general surgeons in Trafford Health Authority. When compared with other series, delay to diagnosis has been shortened, particular general practitioner and hospital delay. Fewer patients presented as emergencies and a greater proportion of patients had early-stage disease. There was no significant difference in delay times between Dukes' stage B and C patients but there was a significant difference in survival at 2 years between these two stages. Delay times for patients with risk factors, family histories or diverticular disease were not significantly different from times in patients without these factors.