| 1. |
- Andersson, Ellen, et al.
(författare)
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GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs
- 2017
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Ingår i: Clinical Practice. - : Future Medicine. - 2044-9038 .- 2044-9046. ; 14:3, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.
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| 2. |
- Bourghardt Peebo, Beatrice, 1968-, et al.
(författare)
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Expression of the focal adhesion protein PINCH in normal and alkali-injured corneas and the role of PMNs
- 2007
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 85:4, s. 395-400
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the role of particularly interesting new cysteine-histidine-rich protein (PINCH) in corneal wound healing and early neovascularization and to assess the influence of granulocytes. Methods: A standardized corneal alkali wound was inflicted under general anaesthesia to the right eye of 14 New Zealand White rabbits. Seven of the rabbits received i.v. 5 mg/kg fucoidin every 2 hours to prevent granulocytes from entering the wound area. After 36 hours, the rabbits were killed, the corneas excised, fixed in 4% formaldehyde and embedded in paraffin. The sections were double-stained with antibodies against PINCH and with haematoxylin. Results: In the normal cornea and limbus, PINCH was weakly expressed in the corneal epithelium and in a wedge of the conjunctival stroma. In the wounded corneas, PINCH expression was seen in the frontline of repopulating endothelial and epithelial cells, and in active keratocytes. The vascular endothelium and the granulocytes expressed PINCH, as did the conjunctival epithelium. In the fucoidin-treated rabbits, PINCH expression was markedly reduced. The vascular endothelial cells and the few granulocytes did not express PINCH in these rabbits. Conclusions: PINCH is only slightly expressed in the normal cornea. A corneal wound induces PINCH expression in the repopulating cells, in the vascular endothelial cells of the limbus, in the limbal epithelium and in the granulocytes. Exclusion of granulocytes reduces expression of PINCH and there is no expression at all in the vascular endothelium. © 2007 The Authors Journal compilation 2007 Acta Ophthalmol Scand.
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| 3. |
- Holmqvist, Annica, 1974-
(författare)
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Biological and histological factors as predictors in rectal cancer patients : A study in a clinical trial of preoperative radiotherapy
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With improved surgical techniques and preoperative radiotherapy (RT) the local recurrence rate in rectal cancer patients has been reduced, however the mortality rate is still high and there is a huge variation in the response to preoperative RT in patients with the same tumour stage. To improve patient’s survival, it is of great importance to identify good prognostic and predictive factors that help us to select the best suited patients for preoperative RT in the future.For many years, studies of neoplastic transformation have mainly focused on tumour cells. In recent years, researchers have realised that the stroma around tumour cells and their extracellular matrix components also play an important role in tumour carcinogensesis.The aim of this thesis was to investigate the biological factors, survivin and particularly interesting new cysteine-histidine rich protein (PINCH), histological factors, inflammatory infiltration, fibrosis, necrosis, mucinous content, angiogenesis and lymphangiogenesis as well as their relationships to preoperative RT and to clinical variables in rectal cancer patients who participated in a Swedish rectal cancer trial of preoperative RT.In paper I, the expression of survivin and its relationship to preoperative RT and clinical factors were investigated in 98 primary rectal tumours and adjacent normal mucosa. In all patients, positive survivin expression was independently related to worse survival compared to negative survivin expression in a multivariate analysis.In paper II, PINCH expression and its relationship to RT, clinical, histological and biological factors were investigated at the invasive margin and inner tumour area in 137 primary rectal tumours and in cell line of fibroblasts. In patients without RT, strong PINCH expression was independently related to worse survival in a multivariate analysis. No survival relationship was found in the patients with RT, and there was no difference in PINCH expression between the subgroups of non-RT and RT at the invasive margin/inner tumour area. In patients with RT, strong PINCH expression at the inner tumour area was related to a high level of lymphatic vessel density (LVD).In paper III, the frequency of LVD/blood vessel density (BVD) was analysed at the periphery, the inner tumour area and the invasive margin of 138/140 primary rectal tumours and correlated to RT, clinical, histological and biological factors. In all patients, LVD at the periphery of the tumour was independently related to better survival compared to LVD at the inner tumour area/invasive margin. In all patients, a higher LVD at the periphery was related to negative (wild type) p53 expression.In paper IV, the inflammatory infiltration, fibrosis, necrosis and mucinous content were studied in relation to RT, clinical and biological parameters in preoperative biopsies (n = 153) and in primary tumours (n = 148). In all patients and in the subgroups of non-RT and RT a higher grade of inflammatory infiltration was independently related to improved survival compared to weak inflammatory infiltration in a multivariate analysis.In this thesis, survivin, PINCH, LVD and inflammatory infiltration are independent prognostic factors in rectal cancer patients who participated in a clinical trial of preoperative RT. This information may help us to improve patient’s survival by selecting the best suited patients for preoperative RT in the future.
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| 4. |
- Holmqvist Knutsen, Annica, 1974-, et al.
(författare)
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PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy : A study in a Swedish rectal cancer trial of preoperative radiotherapy
- 2012
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 12:65
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients. Material and Methods: PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by Western blot. Results: In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (p = 0.03). No survival relationship in patients with RT was observed (p = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (p = 0.68)/inner tumour area (p = 0.49). Conclusions: PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.
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| 5. |
- Knutsen Holmqvist, Annica, 1974-, et al.
(författare)
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Inflammatory infiltration, fibrosis, necrosis and mucinous content in relation to clinicopathological and molecular factors in rectal cancers with or without preoperative radiotherapy.
- 2006
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 16:2, s. 321-327
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Tidskriftsartikel (refereegranskat)abstract
- The association between inflammatory infiltration, fibrosis, necrosis and mucinous content in rectal cancers, and their relationship to preoperative radiotherapy (RT) clinicopathological and biological factors (p53, apoptosis and Cox-2) is not fully characterised. We analysed these histopathological parameters and their relationships in rectal cancer patients who participated in a clinical trial of preoperative RT. One hundred and forty-eight preoperative biopsies and 153 surgically resected tumours were examined. Of the surgical specimens, 81 had surgery alone and 72 received RT before surgery. A higher grade of inflammatory infiltration was related to favourable survival in the whole group of patients (p=0.004, for multivariate analysis p=0.01) as well as in the subgroups of patients with (p=0.04) or without RT (p=0.01). After RT, tumours showed a decreased infiltration (p=0.0003) and increased necrosis (p=0.006), strong necrosis was related to favourable survival (p=0.046). Necrosis (p=0.054) and fibrosis (p=0.06) tended to be increased in p53-negative tumours after RT. Inflammatory infiltration was a strong prognostic factor in rectal cancer patients, regardless of RT. RT tended to induce necrosis and fibrosis in p53-negative tumours.
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| 6. |
- Kotti, Angeliki
(författare)
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Clinical and Biological Factors Related to Survival in Patients with Rectal Cancer
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rectal cancer is a common malignancy within the gastrointestinal tract. Despite the advances in diagnosis and treatment of rectal cancer patients during the last decades, there are still many patients who die from their disease. In order to personalise the therapy and optimise the clinical outcomes, it is important to identify factors that have an impact on survival of rectal cancer patients. Therefore, the overall aim of this thesis was to identify clinical and biological factors that were related to survival in patients with rectal cancer. Paper I aimed to evaluate the impact of statins on survival in older and younger patients with rectal cancer. The study included 238 older patients (≥70 years) and 227 younger patients (<70 years) from the southeast healthcare region of Sweden. The patients were classified as statin users if they used any type of statins at the time of the cancer diagnosis. In the older group, statin users had better cancer-specific survival, disease-free survival, and overall survival compared with non-users. No such association was present in the younger group. Paper II aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients. The study included 173 patients from the region Ostergotland of Sweden who underwent a CT colonography at the time of diagnosis. Skeletal muscle index (SMI) and visceral adipose tissue area (VAT) were quantified at the level of the third lumbar vertebral body, using the CT colonography acquired at the time of diagnosis. The patients were divided into a low or high SMI group, and a low or high VAT group. Low SMI was related to worse survival compared to high SMI in all the patients. High VAT was related to better survival in men with low or middle rectal cancer, while high VAT was related to worse survival in women with low or middle rectal cancer. Paper III aimed to evaluate the prognostic value of SPARCL1 expression in patients with rectal cancer with a focus on radiotherapy (RT). The study included 138 patients with rectal cancer who participated in the Swedish Rectal Cancer Trial. Of those, 63 patients underwent both preoperative RT and surgery, while 75 patients had surgery alone. SPARCL1 expression was determined by immunohistochemistry. Strong SPARCL1 expression was related to better overall survival compared to weak SPARCL1 expression in patients with stage III disease who received RT, but not in patients with stage III disease who did not receive RT. Moreover, SPARCL1 expression was increased in primary tumours with RT compared to tumours without RT. In summary, statin use was related to improved survival in older patients with rectal cancer. CT-measured body composition parameters provided useful information for determining the prognosis of rectal cancer patients. SPARCL1 was identified as a potential prognostic biomarker in rectal cancer patients who received preoperative RT. Conclusively, the results of this thesis indicate that statin drugs, CT-measured body composition and SPARCL1 are factors related to survival in patients with rectal cancer. The evidence may benefit patients by more accurate estimating of their prognosis, personalised treatment and improved clinical outcomes.
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| 7. |
- Kotti, Angeliki, et al.
(författare)
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Computed tomography-measured body composition and survival in rectal cancer patients: a Swedish cohort study
- 2022
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Ingår i: Cancer & Metabolism. - : BMC. - 2049-3002. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The association between body composition and survival in rectal cancer patients is still unclear. Therefore, we aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients, stratifying our analyses by sex, tumour location, tumour stage and radiotherapy. Methods This retrospective cohort study included 173 patients with rectal adenocarcinoma. CT colonography scans at the time of diagnosis were used to assess the skeletal muscle index (SMI) and the visceral adipose tissue area (VAT). The patients were divided into a low or high SMI group and a low or high VAT group according to previously defined cutoff values. Endpoints included cancer-specific survival (CSS) and overall survival (OS). Results In all patients, low SMI was associated with worse CSS (HR, 2.63; 95% CI, 1.35-5.12; P = 0.004) and OS (HR, 3.57; 95% CI, 2.01-6.34; P < 0.001) compared to high SMI. The differences remained significant after adjusting for potential confounders (CSS: adjusted HR, 2.28; 95% CI, 1.13-4.58; P = 0.021; OS: adjusted HR, 3.17; 95% CI, 1.73-5.82; P < 0.001). Low SMI was still related to a poor prognosis after stratifying by sex, tumour location, stage and radiotherapy (P < 0.05). High VAT was associated with better CSS (HR, 0.31; 95% CI, 0.11-0.84; P = 0.022) and OS (HR, 0.40; 95% CI, 0.17-0.97; P = 0.044) compared to low VAT among men with rectal cancer <= 10 cm from the anal verge. High VAT was associated with worse CSS (HR, 4.15; 95% CI, 1.10-15.66; P = 0.036) in women with rectal cancer <= 10 cm from the anal verge. Conclusions Low SMI was associated with worse survival. High VAT predicted better survival in men but worse survival in women. The results suggest that CT-measured body composition is a useful tool for evaluating the prognosis of rectal cancer patients and demonstrate the need to include the sex and the tumour location in the analyses.
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| 8. |
- Kotti, Angeliki, et al.
(författare)
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Survival benefit of statins in older patients with rectal cancer : A Swedish population-based cohort study
- 2019
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Ingår i: Journal of Geriatric Oncology. - : Elsevier. - 1879-4068 .- 1879-4076. ; 10:5, s. 690-697
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesIncreasing evidence suggests that statins may have antitumor effects but their rolein rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer.Materials and MethodsThis study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013.ResultsIn the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19–0.72; P = .003; OS: HR, 0.62; 95% CI, 0.39–0.96; P = .032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06–0.59; P = .005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P = .043; log-rank P = .028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P = .032). No such association was present in the younger group.ConclusionStatin use was related to improved survival in older patients with rectal cancer.This observation is important given the low cost and safety of statins as a drug.
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| 9. |
- Yndigegn, Troels, et al.
(författare)
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Safety of early hospital discharge following admission with ST-elevation myocardial infarction treated with percutaneous coronary intervention: a nationwide cohort study
- 2022
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Ingår i: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. - : European Society of Cardiology. - 1969-6213 .- 1774-024X. ; 17:13, s. 1091-1099
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Second Primary Angioplasty in Myocardial Infarction (PAMI-II) risk score is recommended by guidelines to identify low-risk patients with ST-elevation myocardial infarction (STEMI) for an early discharge strategy. AIMS: We aimed to assess the safety of early discharge (≤2 days) for low-risk STEMI patients treated with primary percutaneous coronary intervention (PCI). METHODS: Using nationwide data from the SWEDEHEART registry, we identified patients with STEMI treated with primary PCI during the period 2009-2017, of whom 8,092 (26.4%) were identified as low risk with the PAMI-II score. Low-risk patients were stratified according to their length of hospital stay (≤2 days vs >2 days). The primary endpoint was major adverse cardiovascular events (MACE, including death, reinfarction treated with PCI, stroke or heart failure hospitalisation) at one year, assessed using a Cox proportional hazards model with propensity score as well as an inverse probability weighting propensity score of average treatment effect to adjust for confounders. RESULTS: A total of 1,449 (17.9%) patients were discharged ≤2 days from admission. After adjustment, the one-year MACE rate was not higher for patients discharged at >2 days from admission than for patients discharged ≤2 days (4.3% vs 3.2%; adjusted HR 1.31, 95% confidence interval [CI]: 0.92-1.87, p=0.14), and no difference was observed regarding any of the individual components of the main outcome. Results were consistent across all subgroups with no difference in MACE between early and late discharge patients. CONCLUSIONS: Nationwide observational data suggest that early discharge of low-risk patients with STEMI treated with PCI is not associated with an increase in one-year MACE.
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