Gudrun Lindmark

The Swedish rectal cancer registry

An audit of all patients with rectal cancer in Sweden was launched in 1995. This is the first report from the Swedish Rectal Cancer Registry (SRCR).

Prognostic value of p53 genetic changes in colorectal cancer.

PURPOSE To explore whether there is a linkage between different mutations in the p53 gene in primary colorectal cancer and the risk of death from colorectal cancer in a large group of patients with long follow-up. We also compared a complementary DNA-based sequencing method and an immunohistochemical (IHC) method for detecting p53 protein overexpression in colorectal cancer. MATERIALS AND METHODS The entire coding region of the p53 gene was sequenced in 191 frozen tumor samples collected from January 1988 to November 1992. RNA was extracted and synthesized to cDNA. p53 was amplified by the polymerase chain reaction, and the DO-7 monoclonal antibody was used in the IHC assessments. RESULTS Mutations were detected in 99 samples (52%) from 189 patients. There was a significant relationship between the p53 mutational status and the cancer-specific survival time, with shorter survival time for patients who had p53 mutations than for those who did not (P = .01, log-rank test). Mutations outside the evolutionarily conserved regions were associated with the worst prognosis. Multivariate analysis showed that the presence of p53 mutations was an independent prognostic factor (relative hazard, 1.7, P = .03). There was no significant relationship between overexpression of p53 protein, as determined by IHC analysis, and cancer-specific survival. CONCLUSION Mutational analyses of the p53 gene, using cDNA sequencing in colorectal cancer, provide useful prognostic information. In addition, cDNA sequencing gives better prognostic information than IHC assessment of p53 protein overexpression.

Prognostic predictors in colorectal cancer

PURPOSE: Better prognostic predictors in colorectal cancer than the Dukes stage are necessary for individualized therapy and follow-up. METHODS: Survival among 212 patients operated on for colorectal cancer was examined regarding various clinical, histopathologic, cellular, and serologic tumor characteristics. RESULTS: Beside the Dukes stage, which was the most powerful variable, the erythrocyte sedimentation rate, leukocyte blood count, alkaline phosphatase, aspartate aminotransferase, six different serum tumor markers, number of small blood vessels, and age were found to be significantly associated with survival. The leukocyte blood count, alkaline phosphatase, and aspartate aminotransferase retained their significance in a multivariate model including tumor differentiation, local tumor stage, and age. Inclusion of tissue polypeptide antigen, the most powerful tumor marker in the multivariate model, showed that only the tumor stage, tissue polypeptide antigen, and age were statistically significantly correlated to survival. This was valid both for the group of patients considered as potentially curable and for those who potentially have been cured (Dukes Stages A-C). CONCLUSIONS: A great number of prognostic predictors failed to discard Dukes stage as the best one. One serum tumor marker, tissue polypeptide antigen, contains independent additional prognostic information.

Risk factors of rectal cancer local recurrence: population-based survey and validation of the Swedish rectal cancer registry

Aim  Despite advances in rectal cancer treatment, local recurrence (LR) remains a significant problem. To select high‐risk patients for different treatment options aimed at reducing LR, it is essential to identify LR risk factors.

Anastomotic leakage after surgery for rectal cancer: a risk factor for local recurrence, distant metastasis and reduced cancer-specific survival?

Aim  The impact of anastomic leakage (AL) on the oncological outcome after anterior resection (AR) for rectal cancer is still controversial. We explored the impact of AL regarding local recurrence (LR), distant metastasis and overall recurrence (OAR). Overall and cancer‐specific survival was analysed.

Time trends, improvements and national auditing of rectal cancer management over an 18-year period.

The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population‐based data for appraisal of external validity in selected patient series.

COL11A1 in FAP polyps and in sporadic colorectal tumors

BackgroundWe previously reported that the α-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of β-catenin.MethodsWe used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/β-catenin pathway.ResultsIn this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/β-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas.ConclusionsOur results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/β-catenin pathway in FAP and sporadic colorectal cancer.

The Impact of Hospital Volume on Surgical Outcome in Patients with Rectal Cancer

PURPOSE: This study was designed to investigate, in a population-based setting, the surgical outcome in patients with rectal cancer according to the hospital volume. METHODS: Since 1995 all patients with rectal cancer have been registered in the Swedish Rectal Cancer Registry. Hospitals were classified, according to number treated per year, as low-volume, intermediate-volume, or high-volume hospitals (<11, 11–25, or >25 procedures per year). Postoperative mortality, reoperation rate within 30 days, local recurrence rate, and overall five-year survival were studied. For postoperative morbidity and mortality the whole cohort from 1995 to 2003 (n = 10,425) was used. For cancer-related outcome only, those with five-year follow-ups, from 1995 to 1998, were used (n = 4,355). RESULTS: In this registry setting the postoperative mortality rate was 3.6% in low-volume hospitals, and 2.2% in intermediate-volume and high-volume hospitals (P = 0.002). The reoperation rate was 10%, with no differences according to volume. The overall local recurrence rates were 9.4%, 9.3%, and 7.5%, respectively (P = 0.06). Significant difference was found among the nonirradiated patients (P = 0.004), but not among the irradiated patients (P = 0.45). No differences were found according to volume in the absolute five-year survival. CONCLUSION: Postoperative mortality and local recurrence in nonirradiated patients were lower in high-volume hospitals. No difference was seen between volumes in reoperation rates, overall local recurrence, or absolute five-year survival.

Clinicopathologic Factors Identify Sporadic Mismatch Repair–Defective Colon Cancers

Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers were linked to MMR status based on immunostaining and BRAF mutation status.MMR defects were identified in 22.7% of the tumors, with 46 classified as sporadic. When the clinical parameters of age, sex, and proximal tumor location were combined with the morphologic features with the highest relative risks (RRs), eg, mucinous differentiation (RR, 9.0), tumor-infiltrating lymphocytes (RR, 7.5), absence of necrosis (RR, 7.5), and expanding growth pattern (RR, 5.0) into a 7-factor index, the presence of at least 4 features identified the MMR-defective tumors with 92.3% sensitivity and 75.3% specificity and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers.

Validity of the Swedish Rectal Cancer Registry for patients treated with major abdominal surgery between 1995 and 1997

Abstract Background. Founded in 1995, the Swedish Rectal Cancer Registry (SRCR) is frequently used for rectal cancer research. However, the validity of the registry has not been extensively studied. This study aims to validate a large amount of registry data to assess SRCR quality. Material and methods. The study comprises 906 patients treated with major abdominal surgery registered in the SRCR between 1995 and 1997. SRCR data for 14 variables were scrutinized for validity against the medical records. Kappas and Kendalls correlation coefficients for agreement between SRCR data and medical records data were calculated for 13 variables. Results. For 11 variables, concerning the tumor, neoadjuvant therapy, the surgical procedure, local radicality and TNM stage, data were missing in 5% or less of the registrations; for the remaining three variables, anastomotic leakage, local and distant recurrence, data were missing in 13–38%. For the variables surgery performed or not and type of surgical procedure, no data were missing. Erroneous registrations were found in less than 10% of all variables; for the variables preoperative chemotherapy and surgery performed or not, all registrations were correct. For the variables concerning neoadjuvant therapy, local radicality according to the surgeon as well as the pathologist and distant metastasis, the false-positive or -negative registrations were equally distributed, and for the variables rectal washout, rectal perforation, anastomotic leakage and local recurrence there was a discrepancy in distribution. The correlation coefficient for 12 variables ranged from 0.82 to 1.00, and was 0.78 for the remaining variable. Conclusion. The validity of the SRCR was good for the initial three registry years. Thus, research based on SRCR data is reliable from the beginning of the registrys use.