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- Arbman, Gunnar
(författare)
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Colorectal cancer in Östergötland : risk factors, diagnosis, and quality of treatment
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this investigation colorectal cancer in the county of Östergötland has been studied with emphasis on risk factors, diagnostic efforts, and the results of treatment.In two case-control studies on food and colorectal cancer, a decreased risk was associated with a high intake of cereal fibre, total fibre, and calcium per unit energy consumed as well as a high intake of raw vegetables. Processed meat was associated with an increased lisk for colon cancer and alcohol with an increased risk for rectal cancer. Drug consumption was also found to influence the cancer risk.In a case-control study on occupational factors and the risk for colorectal cancer, some occupations seemed to influence the risk for colon and rectal cancer in different ways. Twenty years of physically active work significantly decreased the risk for left-sided colon cancer but increased the risk for rectal cancer. Accordingly, twenty year of sedentary work significantly decreased the risk for rectal cancer.Known risk factors were found in 12% of colorectal cancer patients, though previous cholecystectomy did not turn out to be a risk factor.The symptoms of colon cancer are vague and unspecific, whereas bleeding is prominent and a dominating symptom in rectal cancer. Conflicting results have been presented regarding the importance of a short delay between onset of symptoms and treatment. In our study, a more favourable stage distribution was found for rectal cancer with a very short delay between start of symptoms and treatment, but not for colon cancer.Results of treatment for colorectal cancer show considerable variation in different series, which can be due to differences in selection and classification as well as in treatment. A computerized system for quality assurance of colorectal cancer was introduced in Östergötland in 1984. All cases diagnosed 1984-1986 were registered in this system, making it possible to study outcome of treatment for an unselected population. The results of treatment in terms of postoperative mortality and five year survival were comparable to the results from specialised international centres, but local recunence rate after operation for rectal cancer was high (20%).To reduce this local recurrence rate, the technique of total mesorectal excision was introduced in three of the surgical departments in the county. Using the system for quality assurance, the local recunence rate during a three year period before the change in technique was compared with a three year period when the new technique was used. The local recunence rate was significantly reduced in the later period without any change in postoperative complications.In conclusion this study shows an environmental influence on cancer-risk that may be different for colon and rectal cancer. The usefulness of a continuous quality assurance system to detect shmtcomings in diagnosis and treatment and to evaluate new techniques is also shown. Finally, total mesorectal excision reduces the local recurrence rate for rectal cancer in an unselected population treated in different kinds of hospital.
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- Jansson, Agneta K., et al.
(författare)
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The BH3-only member Noxa may not be involved in the development of unselected colorectal cancer
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Noxa is an BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Further, we searched for mutations in the Noxa gene using single stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumours and decreased in 9% and increased in 16% of the tumours compared to the normal mucosa, but these changes did not have any clinical or pathological significance. We did not find any mutations in the gene. Thus, our observations suggest that the variations in Noxa gene may not be of particular importance in the development of unselected colorectal cancer.
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- Lewander, Andreas, et al.
(författare)
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NF-κB p65 phosphorylated at Serine-536 is an independent prognostic factor in Swedish colorectal cancer patients
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: NF-κB transcription factor protein family has diverse cellular and biological functions, and post-translational modification is important to regulate these functions. An important site of phosphorylation of p65 subunit is at Serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization and protein stability. In this study, we investigated a phospho-Ser536-p65 in colorectal cancers and its relationship to clinicopathological factors of the patients. Materials and Methods: Expression of phospho-Ser536-p65 was examined by using immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens and 18 metastases in the lymph nodes. Results: The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumour (p<0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumours correlated with worse survival of the patients independent of gender, age, tumor location, stage and differentiation (p=0.04, hazard ratio 1.89, 95% CI 1.03-3.47). Conclusion: The NF-κB p65 subunit phosphorylated at Serine-536 is anindependent prognostic factor in colorectal cancer patients.
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| 8. |
- Loftås, Per, 1964-
(författare)
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Response to neoadjuvant treatment in rectal cancer surgery
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.
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- Shabo, Ivan, et al.
(författare)
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Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patients
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- CD163 is a macrophage specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression, as a macrophage trait, and macrophage infiltration and their clinical-pathological significance in colorectal cancer. The hypothesis of macrophage-cancer cell fusion may explain the expression of CD163 in cancer cells. Immune-staining of CD163 and macrophage infiltration were evaluated in paraffinembedded specimens, earlier analyzed for Ki-67, CD31 and D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 77 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data. CD163 is positive in cancer cells in 16-18% of the patients and it is related to advanced tumor stages (stage III-IV) and unfavorable prognosis. High macrophage infiltration may be related to lower survival but this relation was not statistically significant. The prognostic significance of CD163 expression is independent of tumor stage (p=0,015) and macrophage density in tumor stroma (p=0,007). The expression of macrophage phenotype in colorectal cancer cells is associated with poor prognosis independently of tumor stage and macrophage density in the tumour stroma. Macrophages may promote tumour growth and progression by an autocrine interaction with cancer cells. Macrophage – cancer cell fusion may occur in colorectal cancer and contribute to tumour progression and metastasis.
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