| 1. |
- Angenete, Eva, 1972, et al.
(author)
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Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation
- 2007
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In: International journal of colorectal disease. - 0179-1958. ; 22:6, s. 667-74
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Journal article (peer-reviewed)abstract
- BACKGROUND: In rectal cancer treatment, preoperative radiotherapy has led to reduction of local recurrence, but it is associated with morbidity and increased risk for secondary tumours. Matrix metalloproteinases (MMPs) are associated with tumour progression through tissue remodeling. The aim of this study was to investigate tissue remodeling after preoperative radiotherapy and to explore possible correlations with clinical outcome. MATERIALS AND METHODS: Ninety-one patients scheduled for rectal cancer surgery were included; 49% received preoperative radiotherapy three-field treatment, 5 x 5 Gy. Blood samples and biopsies from tumour and adjacent mucosa were taken during surgery. Biopsies and plasma were assayed with ELISA for MMP-1, MMP-2 and MMP-9. Clinical outcome was reviewed focusing on infections, perineal healing, fistula formation, anastomotic dehiscence, small bowel obstruction, local recurrence and distant metastases. RESULTS: Compared to non-irradiated mucosa, MMP-2 (p < 0.0001), MMP-1 (p = 0.03) and MMP-9 (p = 0.04) were significantly higher in irradiated normal mucosa. Tumour tissue had higher levels of MMP-2 if irradiated (p < 0.0001). A correlation between MMP-2 levels and wound infection (p = 0.02) as well as fistula formation (p = 0.04) was found. MMP-1 in mucosa (p = 0.02) and tumour (p = 0.04) were higher in patients developing distant metastases. Plasma levels were not influenced by irradiation, but MMP-2 was higher in patients who were later developing distant metastases (p = 0.007). CONCLUSIONS: Extracellular matrix remodeling after radiotherapy seems to be correlated to postoperative morbidity; MMP-2 is associated with both wound infections and fistula formation. High levels of MMP-1 in tumour and mucosa as well as MMP-2 in plasma may be correlated to risk of developing distant metastases.
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| 2. |
- Angenete, Eva, 1972, et al.
(author)
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Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients
- 2007
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In: Int J Colorectal Dis. - 0179-1958. ; 11, s. 1331-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Rectal cancer patients are treated with surgery and sometimes radiotherapy. Transforming growth factor-beta1 (TGF-beta1) acts both as an inhibitor of tumour growth and as a promoter of tumour progression. The aim of this study was to determine the levels of TGF-beta1 in tumour tissue, adjacent mucosa and plasma in rectal cancer patients and relate these to the effect of radiotherapy and clinical outcome. MATERIALS AND METHODS: One hundred and ten patients scheduled for rectal cancer surgery were included, 49% received pre-operative radiotherapy three-field treatment 5 x 5 Gy. Blood samples and biopsies were taken during surgery and later assayed with enzyme-linked immunosorbent assay for total TGF-beta1 and active TGF-beta1. Patients were then followed for 3 years. RESULTS: Total and active TGF-beta1 was higher in tumour tissue compared with rectal mucosa (p < 0.0001). Active TGF-beta1 in tumour tissue and rectal mucosa was lower in the irradiated group (p = 0.007; p < 0.0001). Total TGF-beta1 was higher in patients with metastases at primary diagnosis (p = 0.005) compared to patients without. In patients who later developed metastases, the levels of active TGF-beta1 in plasma were lower (p = 0.004). Local recurrence was associated with lower levels of total TGF-beta1 in the rectal mucosa (p = 0.038). CONCLUSIONS: Higher levels of total TGF-beta1 in tumour tissue at surgery may be indicative of distant metastases, and low levels of active TGF-beta1 in plasma may indicate a risk of developing secondary metastases. Lower levels of total TGF-beta1 in rectal mucosa may influence risk of local recurrence. Measurement of TGF-beta1 in rectal cancer patients may be of clinical use in the future.
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| 3. |
- Angenete, Eva, 1972, et al.
(author)
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uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome.
- 2009
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In: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 153:1, s. 46-53
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is well known that the fibrinolytic system is of importance in inflammation, wound healing, and fibrosis development. However, it is also important in the process of tumor invasion and metastasis. We have investigated protein levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in rectal cancer and effects of radiotherapy, links to clinical outcome, and potential use as prognostic factors. MATERIALS AND METHODS: Ninety-one patients with rectal cancer were studied. Blood samples and biopsies were taken during surgery and assayed with enzyme-linked immunosorbent assay for uPA and PAI-1, and patients were followed prospectively (0-96 mo). RESULTS: Higher levels of uPA (P < 0.0001) and PAI-1 (P < 0.0001) were found in tumor compared with mucosa. Mucosa exposed to radiotherapy had higher levels of uPA (P < 0.0001) and of PAI-1 (P < 0.0001). Irradiated tumor tissue had higher levels of PAI-1 (P < 0.001). PAI-1 in tumor was correlated with T stage (P < 0.001) and N stage (P < 0.01). PAI-1 in plasma was higher in patients with synchronous distant metastases (P < 0.001). Cox regression was used to identify high levels of PAI-1 in tumor as an independent factor related to short disease-free survival (P < 0.01) and the ratio of uPA/PAI-1 to development of metastases (P < 0.01). CONCLUSIONS: There is a relationship between PAI-1 in plasma and rectal cancer metastases. PAI-1 in tumor tissue is correlated to histopathological data and to outcome of rectal cancer. If these findings can be confirmed in larger trials, there will be a possibility to use PAI-1 as a prognostic factor.
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| 4. |
- Langenskiöld, Marcus, 1972, et al.
(author)
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Differential Prognostic Impact of uPA and PAI-1 in Colon and Rectal Cancer.
- 2009
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In: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1423-0380. ; 30:4, s. 210-220
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Journal article (peer-reviewed)abstract
- Background and Objectives: Degradation of extracellular matrix is important for tumour growth and invasion, which in part is regulated by the plasminogen activation system. The aim of the study was to evaluate the protein expression of urokinase plasminogen activator (uPA) and plasminogen-activating inhibitor-1 (PAI-1) in plasma, tumour-free mucosa and tumour tissue regarding their prognostic value in colon and rectal cancer. Methods: Patients (n = 221) undergoing surgery for colorectal cancer were prospectively included. Samples were assayed by ELISA technique. Results: PAI-1 in tumour tissue (p = 0.006), plasma (<0.0001) and uPA in tumour-free mucosa (p = 0.006) were associated with survival in rectal cancer in univariate analysis. An uPA expression level below 1.1 ng/mg (log rank test, p < 0.0001) in tumour-free mucosa was associated with poor survival in rectal cancer. This was true also for patients without disseminated disease (M(0), p = 0.02). PAI-1 in plasma correlated with metastatic disease (p < 0.0001). uPA and PAI-1 were not associated with survival in either tumour tissue, mucosa or plasma in patients with colon cancer. Conclusions: uPA and PAI-1 have a differential prognostic impact in colon and rectal cancer. Preoperative mucosal uPA and plasma PAI-1 protein expression could possibly be used as prognostic factors in rectal cancer.
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| 5. |
- Langenskiöld, Marcus, 1972, et al.
(author)
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Increased TGF-beta 1 protein expression in patients with advanced colorectal cancer.
- 2008
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In: Journal of surgical oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 97:5, s. 409-15
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Journal article (peer-reviewed)abstract
- INTRODUCTION: There is evidence that TGF-beta 1 plays a role as a tumor suppressor in early disease and has pro-oncogenic effects in advanced tumor stage. The aim of the study was to correlate TGF-beta 1 in plasma and tissue to clinical and pathological parameters in patients with various stages of disease progression. METHODS: One hundred sixty-nine patients who underwent surgery for a colorectal carcinoma were prospectively included. Blood samples, tumor free mucosa and tumor biopsies were assayed. RESULTS: TGF-beta 1 protein expression in tumors increased with increasing T-stage regardless of whether patients with metastatic disease were included or not (P = 0.0006). Patients with metastatic disease showed elevated TGF-beta 1 protein expression in both tumor tissue (P = 0.004) and plasma (P = 0.001) compared to those without metastatic disease. TGF-beta 1 protein expression was higher in the colon compared with the rectum in both tumor tissue and tumor-free bowel (P = 0.03), regardless of whether patients with metastatic disease were included or not. This difference was mainly attributable to a higher TGF-beta 1 protein expression in non-metastatic patients with lymph node positivity (P = 0.005). CONCLUSIONS: Higher TGF-beta 1 protein expression is associated with increasing T-stage and metastatic disease, indicating that TGF-beta 1 is of importance in tumor progression. The localization of the tumor seems to influence the TGF-beta 1 protein expression in patients with tumor cell-positive lymph nodes.
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| 6. |
- Langenskiöld, Marcus, 1972, et al.
(author)
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Intestinal mucosal MMP-1 - a prognostic factor in colon cancer.
- 2013
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In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:5, s. 563-569
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Journal article (peer-reviewed)abstract
- Abstract Objective. There is evidence that transforming growth factor-β1 (TGF-β1) and matrix metalloproteinases (MMPs) play an important role in tumor invasion and progression in colorectal cancer. The aim of this study was to assess their utility in prediction of cancer-specific survival (CSS). Materials and methods. 136 patients undergoing curative surgery for colorectal carcinoma were prospectively included. Samples were taken from tumor and tumor-free intestinal mucosa and ELISA was used to assess protein levels in the tissues. Patients were followed for CSS. The median follow-up time for all included patients was 65 months (range: 45-92). The main outcome measure was CSS. Results. T stage, lymph node involvement and high levels of MMP-1 as well as MMP-9 in tumor-free mucosa tissue were significantly associated with CSS in colon cancer in univariate analysis. This prognostic strength was maintained for MMP-1 and N-status in multivariate analysis. Conclusions. The results indicate that MMP-1 is independently associated with CSS in patients with colon cancer. Furthermore, a possible clinical implication is that MMP-1 protein expression in tumor-free mucosa could identify colon cancer patients with poor CSS in need of more intensified adjuvant treatment.
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| 7. |
- Broeren, M., et al.
(author)
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Psychosocial consequences after screening of abdominal aortic aneurysm among 65 year old men
- 2023
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In: Journal of Vascular Nursing. - 1062-0303. ; 41:3, s. 95-102
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Journal article (peer-reviewed)abstract
- Background: In order to reduce the incidence of abdominal aortic aneurysm rupture and mortality, the Swedish Medical Council has introduced a national abdominal aortic aneurysm (AAA) screening program that offers ultrasound examination of 65-year-old men. Screening programmes of AAA may confer both benefits and harms. The study aim was to investigate the psychosocial consequences of AAA screening among men with screening-detected AAA as compared to men identified as AAA-negative at screening, using an AAA-specific questionnaire. Methods: This cross-sectional study investigated the psychosocial consequences of AAA screening mea-sured with a condition-specific questionnaire. This study focused on the Experience of the Diagnosis and the Screening Procedure in terms of Anxiety, Sense of Dejection and Existential Values. One hundred and fifty-eight men with AAA (63%) and 275 with normal aorta size (55%) completed the diagnosis-specific questionnaire. Results: Ninety-six percent of men with screening detected AAA did not regret the screening examination, the corresponding figure for controls being 99.6%. Seventy percent of AAA patients were surprised that something was wrong in their body. Some (85%) of men with AAA were current or previous smokers, about half of them (45%) felt guilty about it and 78% of the current smokers in the AAA group had considered stopping smoking. Both groups considered changing lifestyle, although at a higher rate (32%) among AAA cases than controls (20%), with differences both in intention to change their ways to exercise ( p = 0.019) and food intake ( p = 0.001). Intergroup differences were identified for the majority of items as captured by the questionnaire where men identified with AAA reported more negative psycho-social consequences for all evaluated items except for the items: Regret of the screening examination ( p = 0.069) and feeling terrified ( p = 0.10). Fifty-one percent of AAA cases stated that they feared rupture, and 12% were anxious about rupture dur-ing sexual activity whereas 57% were worried about rupture during intense physical activity. Conclusion: Men who were diagnosed with AAA reported more psychosocial consequences compared to controls; still only a minority of AAA cases reported psychosocial consequences in greater occurrence. To some degree, men with AAA also feared rupture during various types of activities. There appears to be a need for improved patient information and easy access to caregivers for men with screening-detected AAA, which might help to reduce psychosocial consequences associated with the diagnosis.(c) 2023 Society for Vascular Nursing, Inc. Published by Elsevier Inc. All rights reserved.
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| 8. |
- Langenskiöld, Marcus, 1972, et al.
(author)
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Deep Femoral Vein Reconstruction for Abdominal Aortic Graft Infections is Associated with Low Aneurysm Related Mortality and a High Rate of Permanent Discontinuation of Antimicrobial Treatment
- 2021
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 62:6, s. 927-934
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Journal article (peer-reviewed)abstract
- Objective: Aortic prosthesis infection is a devastating complication of aortic surgery. In situ reconstruction with the neo-aorto-iliac system (NAIS) bypass technique has become increasingly used and is recommended in recent treatment guidelines. The main aim was to evaluate NAIS procedural outcomes when undertaken after previous open or endovascular aortic repair in Sweden.Methods: In this retrospective study, The National Quality Registry for Vascular Surgery (Swedvasc) was used to identify Swedish centres that offered the NAIS bypass procedure for aortic prosthesis infection between 2008 and 2018. Variables of special interest were procedural details, short and long term survival, renal and other complications, and the durtion of antimicrobial treatment.Results: Forty patients (36 males, four females [mean age 69 years], 32 open repairs, seven endovascular aortic repairs [EVAR] and one fenestrated EVAR; 21 presented with aorto-enteric fistula) operated on with NAIS bypass were reviewed. The median time from the primary aortic intervention to the NAIS bypass procedure was 32 months (range 0 – 252 months). Mean ± standard deviation operating time was 645 ± 160 minutes, mean blood loss was 6 277 ± 6 525 mL, mean length of intensive care unit stay was 5.3 ± 3.7 days, and mean length of overall hospital stay was 21.2 ± 11.4 days. Thirty-five patients (88%) had a positive microbial culture; the most commonly isolated pathogen was Candida spp. The majority of patients survived for 30 days (n = 35 [88%]), and 33 (83%) and 32 (80%) patients survived for 90 days and one year, respectively. The number of surviving patients free from antimicrobial treatment at 90 days, six months, and one year was 19 (58%), 29 (88%), and 30 (94%). After a mean long term follow up of 69.9 ± 44.7 months, 20 patients were still alive.Conclusion: The NAIS bypass procedure offered reasonable survival and functional outcomes, and was associated with a high cure rate, defined as freedom from any antimicrobial treatment.
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| 9. |
- Langenskiöld, Marcus, 1972, et al.
(author)
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Increased plasma MMP-2 protein expression in lymph node-positive patients with colorectal cancer
- 2005
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In: International journal of colorectal disease. - 0179-1958. ; 20:3, s. 245-52
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Journal article (peer-reviewed)abstract
- BACKGROUND: Degradation of the extracellular matrix plays an important part during the invasion of cancer cells into the surrounding tissue. The matrix metalloproteinases (MMPs) have a central role in this process as demonstrated in different malignancies. The aim of this study was to investigate the presence of several MMPs from tumour, adjacent tumour-free colon segment and from plasma, in order to evaluate how these factors might be used as predictors in colorectal malignancy. METHODS: Seventy-two patients who underwent surgery because of a colorectal carcinoma were included. Biopsies from the tumour, macroscopically tumour-free bowel and plasma samples were analysed with enzyme-linked immunosorbent assay tests (ELISAs) quantifying protein expression of several MMPs. RESULTS: We found highly elevated concentrations of MMP-1, MMP-2, MMP-3 and MMP-9 protein expression in tumour tissue compared with tumour-free tissue (p<0.0001). Elevated MMP-1 tumour levels were found in patients with Dukes' C cancers (p=0.02). Lymph node status correlated with the expression of MMP-2 in plasma, which was significantly increased in patients with lymph node metastasis compared with those without (p=0.002). MMP-2 in plasma was higher in T3 and T2 tumours than in T4 tumours (p=0.0083). CONCLUSION: The MMPs we investigated were strongly elevated in tumour tissue compared with tumour-free bowel wall. Our results indicate that MMP-2 in plasma may possibly be used as a predictor in colorectal malignancy. The use of MMP-2 as a predicting tool in combination with different imaging techniques may give important preoperative information in patients with colorectal cancer.
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| 10. |
- Langenskiöld, Marcus, 1972, et al.
(author)
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Leukocyte subsets and abdominal aortic aneurysms detected by screening in men
- 2020
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:3, s. 345-355
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Journal article (peer-reviewed)abstract
- Objective: In the present case–control study, we describe the associations between leukocyte subsets in blood and early, screening-detected AAA in men. An abdominal aortic aneurysm (AAA) may result in a life-threatening rupture of the aortic wall. The trigger for AAA formation remains unknown, but the vascular adventitia of advanced AAAs is infiltrated by various leukocytes, indicating that the pathogenesis may involve inflammation. Methods: In Sweden, all 65-year-old men are invited to an ultrasound examination for detection of AAA. At the Gothenburg screening site, 16256 men were examined in 2013–2017, 1.2% of whom had an AAA (diameter of the infrarenal aorta ≥30mm). All men with AAA at screening as well as a randomized selection of AAA-free screened men were invited to participate in a case–control study. Results: The median diameter of AAAs was 33mm. Men with an AAA (n=151) had a higher frequency of smoking, hypertension and statin use than controls (n=224). Blood levels of neutrophils, lymphocytes, monocytes and basophils were higher in individuals with an AAA, but eosinophil count did not differ from controls. Odds ratios (95% confidence interval) for AAA were 8.6 (4.2–17.4), 3.5 (1.9–6.6) and 3.3 (1.8–6.3) for the highest versus lowest quartile of neutrophils, lymphocytes and monocytes, respectively. For neutrophils and lymphocytes, the association with AAA remained significant after adjustment for smoking and other known risk factors/markers. Conclusion: Several, but not all, subsets of circulating leukocytes are associated with screening-detected AAA in men, which is insufficiently explained by associations with smoking and other confounders. © 2020 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine
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