Adjuvant therapy of poor prognosis colon cancer with levamisole: results of an EORTC double-blind randomized clinical trial

From 1978 to 1985, 297 patients were entered in a double-blind randomized trial comparing levamisole to placebo as adjuvant therapy of Dukes' C carcinoma of the colon. Therapy consisted of from two to five tablets of 50 mg levamisole (or placebo) twice a week, depending on bodyweight for 1 year. Levamisole was generally well tolerated, with only four reversible cases of agranulocytosis reported among 129 patients. The trial failed to show a benefit of levamisole on disease-free survival (P = 0.53) or on survival (P = 0.35). There was no difference between the two treatment groups in terms of number of disease relapses, sites of relapse, or time to relapse. The proportion of patients still alive at 5 years was 51 per cent (standard error, 5.5 per cent) in the levamisole group versus 39 per cent (standard error, 5.4 per cent) in the placebo group.     

Pre- versus postoperative radiotherapy in rectal carcinoma: an interim report from a randomized multicentre trial

Since October 1980 a randomized multicentre trial has been in progress among patients with rectal carcinoma, in whom high-dose fractionated pre-operative irradiation (total dose 25.5 Gy in 5-7 days) is being tested against postoperative irradiation to a high dose level using a conventional fractionation scheme (totally 60 Gy in 8 weeks) delivered only to a high-risk group of patients (Dukes' stages B and C). The primary aim of the trial is to investigate whether local recurrence rate differs between the two groups, and a secondary aim is to see whether 5-year survival will differ between the two groups of patients. Up to October 1984, 360 patients have been randomly allocated to these two groups. Locally curative surgery has been performed in 161 patients in the pre-operative irradiation group and in 152 patients in the postoperative irradiation group. Pre-operative irradiation was extremely well tolerated and there were no irradiation-related complications; 95 per cent of these patients received their treatment according to the intended schedule. However, 48 of the 161 patients had a tumour in Dukes' stage A. Pre-operative radiotherapy had no impact on postoperative mortality or the occurrence of anastomosis dehiscence, but significantly more patients with perineal wound sepsis after an abdominoperineal resection were found in the group of patients receiving pre-operative radiotherapy. This prolonged the stay in hospital after surgery. Postoperative radiotherapy was not so well tolerated as pre-operative treatment, and in a substantial number of patients the treatment could not be commenced until a relatively long time after surgery. To date, the local recurrence rate is acceptably low (approximately 10 per cent) in both treatment groups.     

Outcome of patients with rectal cancer treated by stapled anterior resection

The mortality, morbidity and long-term survival in stapled anterior resection for rectal carcinoma has been analysed in 74 patients. Twelve patients were Dukes' A, 26 B, 29 C, and 7 'D' (submitted to hepatic resection). Operative mortality rate was 3 per cent. Three patients (4 per cent) had clinical anastomotic leakage. Two patients (3 per cent) developed anastomotic stenosis. Local recurrence was present in three patients (4 per cent). The mean (+/- s.e.m.) overall survival rate at 5 years was 67 +/- 6 per cent. There was no significant difference in survival between Dukes' B and C (70 +/- 10 per cent versus 59 +/- 10 per cent, P = 0.209). Patients with absent local spread had a significantly better 5-year survival rate than those with positive local lymph nodes (80 +/- 7 per cent versus 54 +/- 9 per cent, P less than 0.01). The present results confirm the satisfactory use of the EEA stapler device for colorectal anastomoses in rectal cancer and in patients with resectable liver metastasis.     

'Close shave' in anterior resection

Of 192 anterior resections for rectal cancer performed over 10 years by one author (R.J.H.), 169 (88 per cent) included total mesorectal excision and all included lavage of the clamped distal rectum. Of this series, 152 (79 per cent) were classed as curative, 110 with a resection margin greater than 1 cm and 42 with a resection margin less than or equal to 1 cm. The group with a greater than 1 cm margin had a significantly lower Dukes' A to B ratio than the group with a margin less than or equal to 1 cm, although the proportion with Dukes' C lesions was similar in both groups (chi 2 = 6.712; P = 0.035). There were no local recurrences in the latter group (95 per cent confidence interval (CI) is 0-5.9 per cent) while there were four (3.6 per cent) in the former group (95 per cent CI is 0.8-7.4 per cent). There were no significant differences in recurrence rates, local and distant, between the two groups (Fisher's exact test, P = 0.2). Reduction of resection margin, provided total mesorectal excision and washout is properly performed, does not increase local recurrence or compromise survival.     

Dihydroergotamine/heparin in the prevention of deep-vein thrombosis after total hip replacement. A controlled, prospective, randomized multicenter trial

In a randomized, double-blind, placebo-controlled multicenter trial, the efficacy and safety of dihydroergotamine mesylate/heparin sodium as a prophylactic agent for deep-vein thrombosis were evaluated in 148 patients who were forty years old or more and who underwent total hip replacement. The incidence of venographically proved postoperative deep-vein thrombosis was 52 per cent in the placebo group and 25 per cent in the dihydroergotamine mesylate/heparin sodium group (p = 0.002). Proximal thrombi developed in only 5 per cent and extensive thrombi, in only 10 per cent of the patients who received dihydroergotamine mesylate/heparin sodium. In contrast, proximal thrombi and extensive thrombi developed in 19 and 25 per cent, respectively, of the patients in the placebo group (p less than 0.05). Adverse reactions in the two groups did not differ significantly: in the treatment group they consisted primarily of hematoma at the site of injection (9 per cent), hematoma at the wound (5 per cent), and excessive postoperative bleeding, and in the placebo group there was hematoma at the site of injection (3 per cent). It was concluded that the combination agent dihydroergotamine mesylate/heparin sodium was effective and safe prophylaxis against deep-vein thrombosis for the patients who underwent total hip replacement in this study.     

Squamous cell carcinoma of the bladder.

Clinical and morphological features of 90 cases of squamous cell carcinoma of the bladder have been reviewed. The lesions were solitary in 90 per cent of the patients, developed without a history of vesical malignant disease in 82 per cent and were invasive at the time of diagnosis in all cases. Ureteral obstruction was demonstrated in 42 per cent of the group. The over-all survival rate at 5 years was only 10.6 per cent. There were 17 patients who received no therapy, all of whom were dead before 2 years. Unassisted supervoltage radiation therapy for patients with stages B2 and C lesions yielded a 5-year survival rate only 17.7 per cent. However, preoperative radiotherapy followed by simple total cystectomy and urinary diversion in a small number of patients with stages B2 and C lesions resulted in a 5-year survival rate in excess of 34 per cent. We are encouraged by this finding and believe that combination therapy warrants further clinical trial.     

Transdermal nitroglycerin in angina pectoris

Stress is sometimes involved in cardiac patients when a number of different drugs are necessary for treatment that are taken in a variety of dose regimes. Any new method for drug delivery that can relieve some of this stress is therefore of interest. Such a preparation is glyceryl trinitrate (GTN) in the form of a skin patch (Transiderm-Nitro) and this was compared to placebo in a double-blind cross-over trial. Following a one-week control period, patients were randomly allocated to three weeks treatment with placebo followed by three weeks with Transiderm-Nitro (1–15 mg in 24 h) or vice versa. Analysis was performed on 77 cases, 37 in the placebo first group (group A) and 40 in the Transiderm-Nitro first group (group B). Irrespective of treatment order, mean weekly anginal attack rates and GTN requirements were significantly less on the active patch than on placebo. Thus, there was a 21 per cent reduction in anginal attacks on placebo but 53 per cent reduction on Transiderm-Nitro (p<O.OOl); while the mean GTN requirement was reduced by 29 per cent on placebo but 56 per cent on Transiderm-Nitro (p<O.OOl). There were no significant changes in pulse rate or recumbent or upright blood pressure. Patients' preferences (blind) were in favour of Transiderm-Nitro (p<O.OOl). The most frequent side-effect was headache, which occurred in 22 per cent of patient; on Transiderm-Nitro but in only 3 per cent on placebo (p<O.Ol). Skin rashes occurred in 5 per cent on Transiderm-Nitro and 4 per cent on placebo (NS). This short-term trial demonstrated highly significant effects from the transdermal GTN preparation in comparison to placebo.     

Prognostic factors and in vitro cytotoxic sensitivity in colorectal cancer

The poor response rates to chemotherapy for colorectal cancer justify attempts to rationalize selection of patients for treatment, and the development of systems to evaluate new cytotoxic agents. Refinement of prognostic indices may identify colorectal cancer patients at a higher risk of recurrence who merit more aggressive treatment. We report our experience with the stem cell assay and pulse thymidine labelling in 43 primary colorectal cancers. Thirty-six tumours were evaluable, and clonogenic growth was obtained in 30 (83 per cent). In 24 tumours (67 per cent) growth was adequate for meaningful interpretation of a cytotoxic drug assay. Frequency of growth and colony forming efficiency did not correlate with histopathological grade, Dukes' stage or tumour cell kinetic indices. Thymidine labelling indices correlated with Dukes' stage (A and B versus C and D, P less than 0.01, Mann-Whitney U test). Cytotoxic assays with 5-fluorouracil and 5'-deoxy-5-fluorouridine were undertaken in 18 cases (14 primary carcinomas, 4 malignant ascites), of which 14 were evaluable and 3/14 (21.5 per cent) were chemosensitive in vitro. Both drugs were equally effective in vitro at clinically attainable plasma concentrations. This is in accordance with the response rates observed clinically with 5-FU chemotherapy in colorectal cancer.     

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.     

Adjuvant therapy for resectable colorectal carcinoma with fluorouracil administered by portal vein infusion. A study of the Mayo Clinic and the North Central Cancer Treatment Group

We randomized 224 patients with resected Dukes' stage B2 or C colorectal cancer to either an untreated control group or to a group receiving 7 days of fluorouracil therapy (500 mg/m2 per day) by portal vein infusion. Randomization was accomplished during surgery after staging by frozen section. Only 5 (2.2%) of our 224 patients were ineligible, but an additional 10 patients assigned to portal vein infusion could not be treated because of technical problems with catheter placement. Toxic reactions were mild. There was only 1 postoperative death on each study arm. At present, the median follow-up for all patients is 5.5 years (range, 1.5 to 9.5 years). Interval to progression and survival curves essentially overlap. The same lack of treatment effect is seen in both the stage B and C subsets.     

Rectal cancer in the Kingdom of Saudi Arabia: the King Faisal Specialist Hospital experience

BACKGROUND: No survival data have yet been published from the Kingdom of Saudi Arabia for patients with rectal cancer. The present paper reports experience with these patients over an 8-year period. METHODS: All patients referred to the King Faisal Specialist Hospital (KFSH) between March 1990 and February 1998 for the primary management of rectal cancer were entered into a computerized database. Prior to 1993 patients did not receive adjuvant therapy. Kaplan-Meier survival curves and the log-rank test were used to compare outcome data. RESULTS: There were 70 men (average age: 55.6 years) and 75 women (average age: 52.8 years). Twelve per cent of patients admitted a family history of colorectal carcinoma (CRC). Twenty-seven per cent of tumours were circumferential. Most tumours were larger than 4 cm and the lowest edge of the majority of tumours was less than 6 cm from the anal verge. Fifty-four per cent of tumours were fixed; 69% of patients received either pre-operative or postoperative radiotherapy. A total of 106 patients underwent 'curative' surgery. Equal numbers of patients had abdomino-perineal resection (APR) and anterior resection (AR) of the rectum. Thirty-five patients received blood peri-operatively (APR, 34%; AR, 12%). Major anastomotic leakage following AR occurred in two patients. Two patients died within 30 days of surgery. Ten patients were lost to follow-up. Following curative AR, eight patients had a distal resection margin of < 2 cm and two patients (Dukes' C) developed local recurrence (25%); 37 patients had a margin > 2 cm and seven developed local recurrence (18.9%). A total of 48 patients underwent curative APR, and four patients developed local recurrence (8.3%). Overall local recurrence was tumour stage-dependent (Dukes' B, 8.8%; Dukes' C, 29.3%). Recurrence was local in 13 patients. Pre-operative radiotherapy seemed to reduce average tumour size (3.6 vs 4.3 cm). The crude overall 5-year survival rate was 39%. The 5-year survival rate for patients with Dukes' stage C cancers following 'curative' surgery was 25%. CONCLUSION: Curative surgery can be performed with a relatively low requirement for blood transfusion, a low mortality and morbidity, and comparable outcomes to Western studies in spite of the large, low and often advanced stage of the tumours managed. Local recurrence rates following curative resection and re-anastomosis for low rectal cancers may be reduced by resisting patient pressure to avoid stomata.     

Salvage cystectomy

This report presents the results of 40 salvage cystectomies performed after failure of radiation therapy to control the disease in patients with bladder cancer. All patients had failure or recurrence after 7,000 rad. The time between end of radiation therapy and cystectomy was three to six months in 11 patients, seven to twelve months in 15, thirteen to twenty-four months in 8, and longer than thirty-six months in 6. There were two immediate and four late postoperative deaths. A total of twenty-two complications occurred in 16 patients. The five-year survival rate was 100 per cent for patients with in situ carcinoma, 58 per cent for Stage A disease, 50 per cent for Stage B1, and 40 per cent for Stage B2 disease. There were no survivors among patients with Stages C and D1 disease. Salvage cystectomy, although associated with significant morbidity, remains a viable form of therapy for patients in whom definitive radiotherapy fails.     

Randomized trial of oral adjuvant razoxane (ICRF 159) in resectable colorectal cancer: five-year follow-up

Razoxane is one of the few agents which has shown activity in the treatment of advanced colorectal cancer. The drug has therefore been evaluated in a prospective randomized controlled trial as an adjuvant to surgery for resectable colorectal cancer. The results to median follow-up of 5 years are reported here. Accrual has ceased and a total of 272 patients entered the trial (133 control, 139 treatment). Treated patients received razoxane postoperatively on a continuous, long-term basis while control patients received identical clinical care but no adjuvant chemotherapy. Analysis of the results shows a significant prolongation of the time to recurrence for Dukes' C patients. All other groups including the overall analysis show no benefit although there is a consistent trend in favour of the treated patients except in Dukes' group 'D'. Razoxane is tolerated well by patients and causes minimal side-effects. However acute leukaemia occurred in three patients (2.45 per cent) after prolonged exposure to the drug and further evaluation should be in patients who are at high risk of developing recurrent cancer, in whom such a risk may be acceptable. It is concluded that razoxane is suitable for further evaluation in colorectal cancer and for incorporation into combination chemotherapy regimens.     

Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes

PURPOSE: In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E(1) prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI. METHODS: The study was randomized, multicenter, double blind, and placebo controlled. Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were randomized to receive placebo or a 60-microg dose of lipo-ecraprost administered intravenously starting 相似文献   

The results of surgical treatment for carcinoma of the rectum of St Mark's Hospital from 1948 to 1972.

The surgical treatment of 3163 patients seen at St Mark's Hospital with a single adenocarcinoma of the rectum in the years 1948-72 is described and the results analysed. In 2948 patients (93-2 per cent) the primary tumour was removed. The operative mortality fell from 7-0 per cent in the years 1948-52 to 2-1 per cent in 1968-72. The proportion of restorative operations has risen steadily over the years to a level of 41-1 per cent in the years 1968-72. There were 2410 operation survivors in the years 1948-67. The crude 5-year survival rate in the whole group was 47-1 per cent (corrected figure 56-7 per cent), and 56-6 per cent (corrected figure 68-4 per cent) for the 1931 survivors of radical operations. Comparison of results for patients surviving radical synchronous combined excision and radical anterior resection shows a significant difference in the two groups: in the former the crude 5-year survival rate was 52-7 per cent (corrected figure 63-8 per cent), and in the latter group the respective figures were 66-7 and 79-4 per cent. A higher proportion of Dukes' A and B cases and of low grade tumours are shown as the pathological background to the more favourable prognosis for patients surviving radical anterior resection.     

A comparison of pre treatment regimens for minimizing the haemodynamic response to blind nasotracheal intubation

The authors determined the cardiovascular effects of blind nasotracheal intubation in four randomized groups of 25 patients each, After induction of anaesthesia with IV thiopentone 4 mg-kg-1, patients in group A received no pretreatment, while patients in group B received IV iidocaine 1.5 mg-kg-1. Three minutes before induction, patients in group C received 0 25 per cent phenylephrine nasal spray (0.2 mg in each nostril); those in group D received ten per cent Iidocaine nasal spray (30 mg in each nostril). After intubation, mean arterial pressures (MAP) were highest in group B (IV Iidocaine) patients (p < 0.05), remaining significantly elevated for 5 min. Conversely, within four minutes after intubation, MAP of group D (ten per cent nasal Iidocaine spray) patients were below control (p < 0.05), and lower than those of any other group (p < 0.05). MAP of group A and C patients increased after intubation, but not as much as in group B patients (p < 0.05). There were no adverse effects from the lidocaine nasal spray. Ten per cent lidocaine nasal spray is a safe and effective way to minimize the MAP increases which typically accompany blind nasotracheal intubation in lightly anaesthetized patients.     

Prophylactic antibiotics in elective colorectal surgery

A randomized prospective study was conducted on 194 patients who underwent elective colorectal surgery for carcinoma. All patients received the same mechanical bowel preparation. In addition, patients in group A received oral neomycin and erythromycin base; patients in group B received systemic metronidazole and gentamicin, while patients in group C received both oral and systemic antibiotics. Postoperative septic complications related to colorectal surgery occurred in 27.4 per cent, 11.9 per cent and 12.3 per cent respectively in groups A, B and C (chi 2 = 7; P less than 0.05). The incidence of sepsis in groups B and C was almost identical. Patients who received oral antibiotics alone (group A) had significantly higher risks of postoperative sepsis when compared with patients in either group B or group C (P less than 0.05). As there is no additional advantage of combining oral and systemic antibiotics, we recommend systemic metronidazole and gentamicin to be used with mechanical bowel preparation in elective colorectal surgery.     

Combined gold seed implantation and external radiotherapy for stage B2 or C prostate cancer

Patients with clinical stage B2 or C prostatic carcinoma represent a group for which there are several treatment options. We followed the course and outcome of 72 patients with clinical stages B and C prostate cancer who were treated with surgical staging, insertion of gold grains and external radiation at our institutions between 1975 and 1984. Of the patients 44 (61 per cent) had clinical stage B disease and the majority (89 per cent) of these were stage B2 lesions. The remaining 28 patients (39 per cent) had clinical stage C tumors. In our series 27 per cent of the clinical stage B and 68 per cent of the clinical stage C cancer patients had positive lymph nodes. The 5-year survival free of disease was 52 per cent for patients with both stages of disease. The 7-year survival free of disease was 47 per cent for patients with clinical stage B and 14 per cent for those with clinical stage C cancer. Lymph node status did not have a statistically significant effect on total survival but survival free of disease correlated significantly with node status. Local treatment failures were defined as patients who required transurethral prostatic resection or orchiectomy for palliation of obstructive symptoms related to local tumor regrowth. By these criteria we prevented local progression in 78 per cent of the patients at 5 years.     

Guideline of surgical treatment of prostatic adenocarcinoma

Based on study of 274 cases of prostate cancer treated in our clinic, selection of patient for radical surgical treatment and choice of procedures were discussed. The radical surgical procedures experienced in our clinic were classified as 31 cases of radical prostatectomy, 4 cases of radical cystoprostatectomy and 7 cases of pelvic exenteration. The endocrine therapy was added to non curative cases postoperatively. In the radical prostatectomy group, the 5-year survival rate of patients with stage A and stage B prostatic adenocarcinoma were 100 and 93 per cent, respectively, and 5-year survival rate of patients who had stage C prostatic adenocarcinoma was 75 per cent. The 5-year survival rates of patients with stage C prostatic adenocarcinoma treated by radical cystoprostatectomy and pelvic exenteration were 50 per cent and 66 per cent, respectively. Cancer recurrence has not seen in the bladder in the patients with stage C prostatic adenocarcinoma treated by radical prostatectomy. Operation of urinary diversion had improved the quality of life. From this data, radical prostatectomy would be indicated for the treatment of patients with stage A, stage B and stage C prostatic adenocarcinoma.     

Studies on the effects of adjuvant chemotherapy on the survival period of patients with colorectal carcinoma

One hundred and eighty nine patients who had undergone curative resection of colorectal cancer were treated with a prospective randomized controlled adjuvant chemo-immunotherapy consisting of Tegafur, Adriamycin (ADM), Mitomycin C (MMC) and OK432. One hundred and thirty five patients with Dukes' B and Dukes' C carcinoma were valid for evaluation. Effects of the therapy were estimated by cumulative survival rate. There was no significant survival difference in colonic carcinoma and Dukes' B rectal carcinoma between the treated and control groups. But there was an advantage in two and three years survival for the chemo-immunotherapy in Dukes' C rectal carcinoma (p less than 0.1). Examining the survival rate of Dukes' C rectal carcinoma for each combination of therapeutic agents, the patients treated with Tegafur and ADM had the most favorable survival rate, the patients treated with Tegafur alone had the next favorable one, the patients treated with Tegafur and MMC had the lowest one. The administration of MMC during operation was less effective than the post operative administration in Dukes' C rectal carcinoma.