Marianne Korsgaard’s research while affiliated with Aarhus University Hospital and other places

Recently, the authors have shown a doubled risk of having an advanced rectal cancer (RC) (Dukes' stage C or D) at the time of treatment, if the interval between onset of symptoms and start of treatment (treatment delay) was >60 days [Korsgaard M, Pedersen L, Sorensen HT, Laurberg S. Treatment delay is associated with advanced stage of rectal cancer but not of colon cancer. Cancer Detect Prev 2006;30(4):341-6]. The authors examined the treatment delay for colorectal cancer (CRC), as influenced by the patients, the general practitioners (G.P.), and the hospitals. Population-based prospective observational study based on 743 Danish CRC-patients. Treatment delay was determined through questionnaire interviews. We examined the patient delay, the G.P. delay, and the hospital delay, and thereby the frequency of patients for whom the Danish fast-track recommendations of a maximum of 14 days to diagnose CRC, and 14 days from the diagnosis to start the of treatment, were met. Colon cancer (CC) and RC-patients were analyzed separately. Patient delay, in particular, was long, and longest for RC-patients (median 44 days vs.18 days). Median G.P. delay was short, but 25% of the CC-patients had a G.P. delay of 59 days or more, and 25% of the RC-patients had a G.P. delay of 53 days or more. The fast-track recommendations were poorly met; 53% of the CC-patients and 39% of the RC-patients waited >14 days after referral for the diagnosis. 29% of the CC-patients, and 53% of the RC-patients waited >14 days before the start of treatment. The total delay was too long, and can be shortened by optimizing all delay intervals.

We used SNP arrays to identify and characterize genomic alterations associated with colorectal cancer (CRC). Laser microdissected cancer cells from 15 adenocarinomas were investigated by Affymetrix Mapping 10K SNP arrays. Analysis of the data extracted from the SNP arrays revealed multiple regions with copy number alterations and loss of heterozygosity (LOH). Novel LOH areas were identified at chromosomes 13, 14 and 15. Combined analysis of the LOH and copy number data revealed genomic structures that could not have been identified analyzing either data type alone. Half of the identified LOH regions showed no evidence of a reduced copy number, indicating the presence of uniparental structures. The distribution of these structures was non-random, primarily involving 8q, 13q and 20q. This finding was supported by analysis of an independent set of array-based transcriptional profiles, consisting of 17 normal mucosa and 66 adenocarcinoma samples. The transcriptional analysis revealed an unchanged expression level in areas with intact copy number, including regions with uniparental disomy, and a reduced expression level in the LOH regions representing factual losses (including 5q, 8p and 17p). The analysis also showed that genes in regions with increased copy number (including 7p and 20q) were predominantly upregulated. Further analyses of the SNP data revealed a subset of the identified alterations to be specifically associated with TP53 inactivation (including 8q gain and 17p loss) and lymph node metastasis status (gain of 7q and 13q). Another subset of the identified alterations was shown to represent intratumor heterogeneity. In conclusion, we demonstrate that uniparental disomy is frequent in CRC, and identify genomic alterations associated with TP53 inactivation and lymph node status.

Dukes' stage is the most important predictor of prognosis of colorectal cancer, but the association between delay of treatment (DT) and Dukes' stage is still controversial. From 1 January 2001 to 31 July 2002, we conducted a population-based prospective observational study based on 733 Danish colorectal cancer patients. DT was determined through questionnaire-interviews, and Dukes' stage was obtained from medical records and pathological forms. DT was classified into three groups: short (0-60 days), intermediate (61-150 days) and long (>150 days) DT. Dukes' stage was classified into two groups: non-advanced (Dukes' stage A or B) and advanced (Dukes' stage C or D) cancer. Using relative risk (RR) the association between DT and stage was estimated, with short delay as the reference group. The RR of advanced cancer was 1.0 (95% confidence intervals (CI): 0.8-1.3) for colon cancer patients with an intermediate DT, and 1.1 (95% CI: 0.9-1.4) for patients with a long DT. For rectal cancer patients the RR of advanced cancer was 1.9 (95% CI: 1.1-3.1) for patients with an intermediate DT and 2.1 (95% CI: 1.3-3.4) for patients with a long DT. DT was strongly associated with advanced stage of rectal cancer, but not of colon cancer.

The primary prognostic factor for colorectal cancer (CRC) is stage. Any association between symptoms, diagnostic delay and stage may have implications for the clinical course of the disease. We examined the association between symptoms and diagnostic delay and between symptoms and stage, and assessed whether the associations differed for colon cancer (CC) and rectal cancer (RC). Population-based prospective observational study based on 733 Danish CRC patients. Diagnostic delay and patients' reported symptoms were determined through questionnaire-interviews. Dukes' stage was obtained from medical records and pathology forms. Diagnostic delay was categorized into three delay groups: < or = 60, 61-150 and > 150 days. Stage was classified into nonadvanced (Dukes' A and B) or advanced (Dukes' C and D) cancers. We calculated the frequency of the most frequently reported initial symptom or symptom complex for CC and RC patients, and evaluated the frequency of patients with different initial symptoms/symptom complexes in the three delay groups. For the most frequent initial symptoms/symptom complexes, we calculated the frequencies according to stage, and estimated the relative risk of having an advanced stage, with 95% confidence intervals. The most frequent initial symptoms/symptom complexes were very vague symptoms for CC and rectal bleeding for RC. For both CC and RC, rectal bleeding was significantly associated with nonadvanced stage. The relative risk of having an advanced cancer was 0.6 for monosymptomatic rectal bleeding and 0.7 for rectal bleeding combined with other symptoms. Initial symptoms of CC were often very vague, making it difficult to identify a precise start date. The most frequent initial symptom/symptom complex for RC - rectal bleeding - was better defined. Rectal bleeding was significantly associated with nonadvanced CC and RC and a significantly decreased relative risk of having an advanced cancer.