Delay of diagnosis and treatment of colorectal cancer--a population-based Danish study.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: The total delay was too long, and can be shortened by optimizing all delay intervals.

Frequent occurrence of uniparental disomy in colorectal cancer.

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.

Delay of treatment is associated with advanced stage of rectal cancer but not of colon cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: DT was strongly associated with advanced stage of rectal cancer, but not of colon cancer.

The influence of lumbar lordosis on spinal fusion and functional outcome after posterolateral spinal fusion with and without pedicle screw instrumentation.

The aim of the current study was to examine the correlation between lumbar lordosis, spinal fusion, and functional outcome in patients suffering from severe low back pain, treated by posterolateral spinal fusion with or without pedicle screw instrumentation. One hundred thirty patients were randomly allocated to posterolateral lumbar fusion with or without Cotrel-Dubousset instrumentation. Functional outcome was assessed preoperatively, and 1 and 2 years postoperatively. Lordosis angles of the lumbar spine and fusion rates were assessed at the 1- and 2-year follow-up. No difference in lordosis angle was found between the two groups at any time. Lordosis was unchanged at 2 years compared with preoperative status in both groups. In the instrumented group, nonunion (23%) was followed by a decrease in lordosis at follow-up (p < 0.05). However, in the noninstrumented group, nonunion (14%) resulted in increased lordosis (p < 0.05). No correlation was found between functional outcome and lordosis angle. The current study showed no correlation between functional outcome and lordosis angle either before or after posterolateral spinal fusion. Use of instrumentation did not influence lumbar spinal alignment compared with noninstrumented fusions. The sagittal alignment was stable both 1 and 2 years after solid fusion. The failure mode of instrumented fusions was a reduced degree of lordosis in contrast to an increased degree of lordosis in patients with noninstrumented fusion.