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| 2. |
- Gaber, Alexander, et al.
(författare)
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High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer
- 2009
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 100:10, s. 1540-1548
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Tidskriftsartikel (refereegranskat)abstract
- Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-specific TATI expression in colorectal cancer, assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent patient cohorts. Kaplan-Meier analysis and Cox proportional hazards modelling were used to estimate time to recurrence, disease-free survival and overall survival. In both cohorts, a high (>50% of tumour cells) TATI expression was an independent predictor of a significantly shorter overall survival. In cohort II, in multivariate analysis including age, gender, disease stage, differentiation grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression was associated with a significantly decreased overall survival (HR=1.82; 95% CI=1.19-2.79) and disease-free survival (HR=1.56; 95% CI=1.05-2.32) in curatively treated patients. Moreover, there was an increased risk for liver metastasis in both cohorts that remained significant in multivariate analysis in cohort II (HR=2.85; 95% CI=1.43-5.66). In conclusion, high TATI expression is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer.
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| 3. |
- Birgisson, Helgi, et al.
(författare)
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Adverse effects of preoperative radiation therapy for rectal cancer : long-term follow-up of the Swedish Rectal Cancer Trial.
- 2005
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Ingår i: Journal of Clinical Oncology. - : American Scoiety of Clinical Oncology. - 0732-183X .- 1527-7755. ; 23:34, s. 8697-8705
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Birgisson, Helgi, 1967-
(författare)
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Cancer of the Colon and Rectum : Population Based Survival Analysis and Study on Adverse Effects of Radiation Therapy for Rectal Cancer
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Swedish Cancer Register was used to determine the relative survival rate in colon and rectal cancer and to estimate the occurrence of second cancers related to radiation therapy for rectal cancer. The Swedish Hospital Discharge Register and hospital records were used to estimate the rate of late adverse effects due to radiation therapy for rectal cancer. The whole Swedish population was the source of the survival studies. Patients participating in the Uppsala Trial and the Swedish Rectal Cancer Trial on radiation therapy for rectal cancer constituted the subjects of the studies on late adverse effects and second cancers.The main results of the survival analysis revealed a significant improvement in the 5-year relative survival rate for both colon and rectal cancer. During the time period 1960-1999, the survival improved from 39.6% to 57.2% in colon cancer and from 36.1% to 57.6% in rectal cancer.Patients irradiated for rectal cancer, in addition to surgery, were at increased risk for a second cancer compared to those treated by surgery alone. This risk increase was mainly found for cancers developing in organs within or adjacent to the irradiated target (relative risk (RR) 2.04; 95% confidence interval (CI) 1.10–3.79). Furthermore, the most important late adverse effects of radiation therapy seem to be those on the gastrointestinal tract, in the form of small bowel obstruction (RR 1.88; 95%CI 1.10–3.20) and abdominal pain (RR 1.92; 95% CI 1.14–3.23). Overall, the benefit of radiation therapy was greater than its drawbacks, as a large reduction in local recurrences and better survival was noted in patients treated preoperatively with irradiation for rectal cancer.In conclusion, significant improvements in the survival of patients with colon and rectal cancers have occurred in the last decades, especially in patients with rectal cancer. These improvements probably are related to advances in surgical and adjuvant treatment. The radiation therapy has several drawbacks, however, including an increased risk of second cancers and of bowel obstruction. This emphasises the need to further improve the radiation technique and to select only those patients for radiation therapy who are most likely to benefit from it.
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| 6. |
- Birgisson, Helgi, et al.
(författare)
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Effects of Centralization of Colorectal Surgery on the Outcome of Patients with Distal Sigmoid Colonic Cancer
- 2009
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Ingår i: Digestive Surgery. - : S. Karger AG. - 0253-4886 .- 1421-9883. ; 26:2, s. 169-175
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 1996, all colorectal surgery in the county of Västmanland, Sweden, was centralized to the central District Hospital in Västerås. A Colorectal Unit was established and modern surgical procedures were introduced. The aim of this study was to analyze the outcome for patients treated surgically for distal sigmoid colonic cancer before and after the centralization. Methods: Hospital records of all patients with distal sigmoid colonic cancer, treated between 1991-1995, group 1 (n = 64), and 1996-2000, group 2 (n = 82), were studied retrospectively. Results: In group 2, there were fewer reoperations (n = 0) than in group 1 (n = 6; p = 0.005) and the postoperative mortality was lower; one in group 2 compared with five in group 1 (p = 0.047). The amount of lymph nodes examined were higher and the length of distal surgical margin longer in group 2. Curatively treated patients in group 2 had better overall survival compared to group 1 (RR 0.56; 95% CI 0.34-0.93). Conclusion: Centralization of colorectal surgery resulted in an improvement of pathologic specimens and a decrease in postoperative reoperations and mortality in patients treated surgically for distal sigmoid colonic cancer. Moreover, the overall survival of curatively treated patients was improved.
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| 7. |
- Birgisson, Helgi, et al.
(författare)
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Late adverse effects of radiation therapy for rectal cancer : a systematic overview
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:4, s. 504-516
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. METHODS: Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5 x 5 Gy radiation therapy with surgery alone. RESULTS: The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. CONCLUSIONS: These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued.
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| 9. |
- Birgisson, Helgi, et al.
(författare)
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Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer
- 2015
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer. Methods: Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis. Results: Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination. Conclusions: The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.
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