Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.
PURPOSE: To analyze the occurrence of subacute and late adverse effects in patients treated with preoperative irradiation for rectal cancer. PATIENTS AND METHODS: The study population included 1,147 patients randomly assigned to preoperative radiation therapy or surgery alone in the Swedish Rectal Cancer Trial conducted 1987 through 1990. Patient data were matched against the Swedish Hospital Discharge Register to identify patients admitted to hospital after the primary treatment of the rectal cancer. Patients with known residual disease were excluded, and patients with a recurrence were censored 3 months before the date of recurrence. Relative risks (RR) with 95% CIs were calculated. RESULTS: Irradiated patients were at increased risk of admissions during the first 6 months from the primary treatment (RR = 1.64; 95% CI, 1.21 to 2.22); these were mainly for gastrointestinal diagnoses. Overall, the two groups showed no difference in the risk of admissions more than 6 months from the primary treatment (RR = 0.95; 95% CI, 0.80 to 1.12). Regarding specific diagnoses, however, RRs were increased for admissions later than 6 months from the primary treatment in irradiated patients for unspecified infections, bowel obstruction, abdominal pain, and nausea. CONCLUSION: Gastrointestinal disorders, resulting in hospital admissions, seem to be the most common adverse effect of short-course preoperative radiation therapy in patients with rectal cancer. Bowel obstruction was the diagnosis of potentially greatest importance, which was more frequent in irradiated than in nonirradiated patients.
The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.
PURPOSE: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short-term regimen of high-dose fractionated preoperative radiotherapy (5 x 5 Gy) reduced the local recurrence rates and improved overall survival. This has had an impact on the primary treatment of rectal cancer. The current study investigated the cost-effectiveness of the new combined approach. METHODS AND MATERIALS: After an 8-year follow-up, in-hospital and outpatient costs related to the treatment of rectal cancer and its complications were analyzed for 98 randomly allocated patients who participated in the SRCT from a single Swedish health care region. The costs were then related to the clinical data from the SRCT regarding complications, local and distant recurrences, and survival. RESULTS: The total cost for a nonirradiated patient was US$30,080 compared with US$35,268 for an irradiated patient. The surgery-alone group had increased costs related to local recurrences, and the radiotherapy group had increased costs for irradiation and complications. With a survival benefit of 21 months (retrieved from the SRCT), the cost for a saved year was US$3654. Sensitivity analyses for different rates of local recurrences, the costs related to complications and less marked survival benefit showed that this figure could vary up to US$15,228. CONCLUSION: The cost for a life-year saved in these data was US$3654. This figure could reach US$15,228 in the most pessimistic setting of the sensitivity tests, a cost still comparable with other well-accepted medical interventions.
Preoperative irradiation with 5 × 5 Gy in randomized trials reduces local recurrence rate and may improve survival in patients with resectable rectal cancer.
The aim of this study was to determine whether the same favorable effects could be observed in a population-based study.
This study was conducted via a retrospective analysis of prospectively collected data from the Swedish Rectal Cancer Registry.
This study examined population-based data from Sweden.
All newly diagnosed rectal cancers in Sweden are reported to the Swedish Rectal Cancer Registry.
Between 1995 and 2001, 6878 patients (stages I-III) were operated on with an anterior resection, an abdominoperineal resection, or a Hartmann's procedure. Short-course irradiation was given to 41% of patients preoperatively. To reduce bias, patients operated on with a Hartmann procedure or older than 75 years were excluded when 5-year survival was analyzed (n = 3466). Tumors were analyzed according to height (0-5 cm, 6-10 cm, 11-15 cm).
Five-year cumulative local recurrence and survival rates.
The 5-year cumulative local recurrence rate was 6.3% (95% CI 5.4-7.4) for patients receiving preoperative irradiation and 12.1% (95% CI 10.8-13.5) for patients not receiving preoperative irradiation. Multivariate analyses indicated the risk of local recurrence was 50% lower for patients receiving preoperative irradiation compared with patients not receiving irradiation (hazard ratio = 0.50; 95% CI 0.40-0.62). Among patients younger than 76 years and operated on with an anterior resection or abdominoperineal resection, the 5-year cumulative survival rate was 0.70 (95% CI 0.69-0.72). Disease-free and overall survivals were higher in irradiated patients, and the difference was statistically significant in low tumors.
In this population-based analysis, the favorable effect of preoperative short-course irradiation on local recurrence rates, seen in randomized trials, was confirmed for the entire Swedish population irrespective of tumor height and stage. Data also suggested an effect on 5-year survival, especially in patients with low tumors (0-5 cm).
Parastomal hernia in patients with a permanent colostomy is common. The aim of this study was to evaluate the reliability of the diagnosis based on clinical examination and to compare this examination with the result of a specially designed questionnaire and computerised tomography (CT) scan.
Forty-one patients operated upon with an abdominoperineal resection due to rectal cancer at three hospitals between 1996 and 2002 were included. At minimum of 4 years after the operation, they underwent clinical examination by two or three independent surgeons, answered a colostomy questionnaire and were offered a CT scan of the abdominal wall.
At Hospital I, 17 patients were examined by three surgeons, with inter-observer kappa values between 0.35 and 0.64. At Hospital II, 13 patients were examined by three surgeons, the kappa values ranged between 0.29 and 0.43. At Hospital III, 11 patients were examined by two surgeons, with kappa value of 0.73. The kappa value between CT scan and the colostomy questionnaire was 0.45.
The inter-observer reliability was low, indicating that parastomal hernia is difficult to diagnose by patient history and clinical examination. Some herniae may not be detected by CT scan, and the correlation to patient-reported complaints is low. A more sensitive radiological method to detect parastomal hernia is needed.
New editions of the TNM staging system for colorectal cancer have been subject to extensive criticism. In the current study, we evaluate each edition of TNM and analyze stage migration caused by the different versions.
Two independent test populations were used: participants derived from a randomized surgical trial from the United Kingdom (n = 455) and patients from a population-based series from Sweden (n = 505). All slides from these patient cases were reviewed with special attention for the presence of tumor deposits. Tumor deposits were classified according to the fifth, sixth, and seventh editions of TNM and correlated with prognosis.
Every change in edition of TNM led to a stage migration of between 33% and 64% in patients with tumor deposits. Reproducibility was best in the fifth edition of TNM. The prognostic value of the seventh edition was best only when all tumor deposits irrespective of size or contour were included as lymph nodes. The prognostic value of the fifth edition was better than that of the sixth.
We demonstrate there is a place for tumor deposits in the staging of patients with colorectal cancer. However, many questions remain about their definition and the reproducibility and use of this category in special situations, such as after neoadjuvant treatment. These should be the subject of additional research before use as a factor in TNM staging. This work demonstrates the necessity of testing modifications before their introduction.
PURPOSE: To analyze the occurrence of second cancers in patients with rectal cancer treated with external radiotherapy (RT) in addition to surgery. PATIENTS AND METHODS: The analyses were based on the Uppsala Trial (completed in 1985), with patients randomly assigned to preoperative RT to all stages or postoperative RT for stage II and III cancers, and the Swedish Rectal Cancer Trial (completed in 1990), with patients randomly assigned to preoperative RT or surgery alone. Patients from the trials were matched against the Swedish Cancer Registry. RESULTS: A total of 115 (7%) of the 1,599 patients developed 122 second cancers. More patients treated with RT developed a second cancer (relative risk [RR], 1.85; 95% CI, 1.23 to 2.78). A significant increased risk for second cancers in the RT group was seen in organs within or adjacent to the irradiated volume (RR, 2.04; 95% CI, 1.10 to 3.79) but not outside the irradiated volume (RR, 1.78; 95% CI, 0.97 to 3.27). For the Swedish Rectal Cancer Trial, 20.3% of the RT patients got either a local recurrence or a second cancer, compared with 30.7% of the non-RT patients (RR, 0.55; 95% CI, 0.44 to 0.70). CONCLUSION: An increased risk of second cancers was found in patients treated with RT in addition to surgery for a rectal cancer, which was mainly explained by an increase in the risk of second cancers in organs within or adjacent to the irradiated volume. However, a favorable effect of radiation seemed to dominate, as shown by the reduced risk of the sum of local recurrences and second cancers.
To examine differences in the relative survival and excess death rates of patients with colorectal cancer in Norway, Sweden and England.
All individuals diagnosed with colorectal cancer (ICD10 (International Classification of Diseases, 10th revision) C18-C20) between 1996 and 2004 in England, Norway and Sweden were included in this population-based study of patients with colorectal cancer. The main outcome measures were 5-year cumulative relative period of survival and excess death rates stratified by age and period of follow-up.
The survival of English patients with colorectal cancer was significantly lower than was observed in both Norway and Sweden. Five-year age-standardised colon cancer relative survival was 51.1% (95% CI 50.1% to 52.0%) in England compared with 57.9% (95% CI 55.2% to 60.5%) in Norway and 59.9% (95% CI 57.7% to 62.0%) in Sweden. Five-year rectal cancer survival was 52.3% (95% CI 51.1% to 53.5%) in England compared with 60.7% (95% CI 57.0% to 64.2%) and 59.8% (95% CI 56.9% to 62.6%) in Norway and Sweden, respectively. The lower survival for colon cancer in England was primarily due to a high number of excess deaths among older patients in the first 3 months after diagnosis. In patients with rectal cancer, excess deaths remained elevated until 2 years of follow-up. If the lower excess death rate in Norway applied in the English population, then 890 (13.6%) and 654 (16.8%) of the excess deaths in the colon and rectal cancer populations, respectively, could have been prevented at 5 years follow-up. Most of these avoidable deaths occurred shortly after diagnosis.
There was significant variation in survival between the countries, with the English population experiencing a poorer outcome, primarily due to a relatively higher number of excess deaths in older patients in the short term after diagnosis. It seems likely, therefore, that in England a greater proportion of the population present with more rapidly fatal disease (especially in the older age groups) than in Norway or Sweden.
Antibiotic resistance is increasing worldwide. The aims of the current study were to determine the fecal carriage of antibiotic-resistant bacteria and antibiotic treatment in surgical patients admitted to hospital due to acute intra-abdominal infections.
Eight Swedish surgical units participated in this prospective multicenter investigation. Rectal swabs were obtained on admission to hospital. Cultures were performed on chromogenic agar and antibiotic susceptibility testing was performed using the disk diffusion method. Extended-spectrum beta-lactamase (ESBL)-phenotype was confirmed by Etest.
Rectal samples were obtained and analyzed from 208 patients with intra-abdominal surgical infections. Surgery was performed in 134 patients (65%). Cephalosporins were the most frequently used empirical antibiotic therapy. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL-producing Enterobacteriaceae were found in samples from 10 patients (5%). Three patients had five E. coli isolates producing AmpC enzymes.
This study shows a high rate of resistance among Enterobacteriaceae against antibiotics which are commonly used in Sweden and should have implications for the future choice of antibiotics for surgical patients.