Marcus Langenskiöld

Endovascular Treatment of Mycotic Aortic Aneurysms A European Multicenter Study

Background— Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection–related complications and long-term survival. Methods and Results— All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39–86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella–positive culture as predictors for late infection–related death. Conclusions— Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella–positive blood cultures were more likely to die from late infection. # CLINICAL PERSPECTIVE {#article-title-32}Background— Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection–related complications and long-term survival. Methods and Results— All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39–86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella–positive culture as predictors for late infection–related death. Conclusions— Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella–positive blood cultures were more likely to die from late infection.

Increased plasma MMP-2 protein expression in lymph node-positive patients with colorectal cancer

BackgroundDegradation 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.MethodsSeventy-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.ResultsWe 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).ConclusionThe 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.

Outcome of the Swedish Nationwide Abdominal Aortic Aneurysm Screening Program

Background: A general abdominal aortic aneurysm (AAA) screening program, targeting 65-year-old men, has gradually been introduced in Sweden since 2006 and reached nationwide coverage in 2015. The aim of this study was to determine the outcome of this program. Methods: Data on the number of invited and examined men, screening-detected AAAs, AAAs operated on, and surgical outcome were retrieved from all 21 Swedish counties for the years 2006 through 2014. AAA-specific mortality data were retrieved from the Swedish Cause of Death Registry. A linear regression analysis was used to estimate the effect on AAA-specific mortality among all men ≥65 years of age for the observed time period. The long-term effects were projected by using a validated Markov model. Results: Of 302 957 men aged 65 years invited, 84% attended. The prevalence of screening-detected AAA was 1.5%. After a mean of 4.5 years, 29% of patients with AAA had been operated on, with a 30-day mortality rate of 0.9% (1.3% after open repair and 0.3% after endovascular repair, P<0.001). The introduction of screening was associated with a significant reduction in AAA-specific mortality (mean, 4.0% per year of screening, P=0.020). The number needed to screen and the number needed to operate on to prevent 1 premature death were 667 and 1.5, respectively. With a total population of 9.5 million, the Swedish national AAA-screening program was predicted to annually prevent 90 premature deaths from AAA and to gain 577 quality-adjusted life-years. The incremental cost-efficiency ratio was estimated to be &OV0556;7770 per quality-adjusted life-years. Conclusions: Screening 65-year-old men for AAA is an effective preventive health measure and is highly cost-effective in a contemporary setting. These findings confirm the results from earlier randomized controlled trials and model studies in a large population-based setting of the importance for future healthcare decision making.

Increased TGF‐Beta1 protein expression in patients with advanced colorectal cancer

There is evidence that TGF‐β1 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‐β1 in plasma and tissue to clinical and pathological parameters in patients with various stages of disease progression.

uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome.

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.

Differential Prognostic Impact of uPA and PAI-1 in Colon and Rectal Cancer

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 (M₀, 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.

Intestinal mucosal MMP-1 - a prognostic factor in colon cancer.

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.

Low Post-operative Mortality after Surgery on Patients with Screening-detected Abdominal Aortic Aneurysms: A Swedvasc Registry Study

OBJECTIVES Screening for abdominal aortic aneurysms (AAAs) substantially reduces aneurysm-related mortality in men and is increasing worldwide. This cohort study compares post-operative mortality and complications in men with screening-detected vs. non-screening-detected AAAs. METHODS Data were extracted from the Swedish National Registry for Vascular Surgery (Swedvasc) for all screening-detected men treated for AAA (n = 350) and age-matched controls treated for non-screening-detected AAA (n = 350). RESULTS There were no differences in baseline characteristics besides age, which was lower in the screening-detected group than in the non-screening-detected group (median 66 vs. 68, p < .001). Open repair was used more frequently than endovascular aortic repair (EVAR) in patients with screening-detected AAAs than in non-screening-detected controls (56% vs. 45% p = .005). No differences in major post-operative complications at 30 days were observed between the groups. In patients treated with open repair there were no differences in 30-day, 90-day or 1-year mortality in screening-detected patients compared to non-screening-detected controls (1.0% vs. 3.2% p = .25, 2.1% vs. 4.5% p = .23, 4.1% vs. 5.8% p = .61). None of the patients treated with EVAR in either group died within 30 days. The 90-day mortality after EVAR was lower in patients with screening-detected AAA than in those with non-screening-detected AAAs (0.0% vs. 3.1%, p = .04). No difference in the 1-year mortality was detected in the EVAR-patients between the two groups (1.4% vs. 4.7%, p = .12). CONCLUSIONS The contemporary post-operative mortality after AAA surgery was low in this national audit of patients with screening-detected AAAs and age-matched controls. Patients with screening-detected AAAs have the same frequency of complications at 30 days as patients with non-screening-detected AAA. This study gives further support to national screening programs for the detection of AAA in men.

Nationwide Experience of Cardio- and Cerebrovascular Complications During Infrainguinal Endovascular Intervention for Peripheral Arterial Disease and Acute Limb Ischaemia

OBJECTIVES Endovascular treatment for peripheral arterial disease (PAD) is increasingly used and also continuously applied to more severe vascular pathology. Only few studies report on systemic complications during these procedures, but it is important to address these risks. We report the results of a recent national audit on cardio- and cerebrovascular complications after endovascular procedures for PAD. METHODS Data from the Swedish Vascular Registry (Swedvasc) were retrieved on all infrainguinal endovascular procedures performed between May 2008 and December 2011. A total of 9187 cases were analysed regarding the prevalence of myocardial infarction and major stroke within 30 days post-intervention. A literature review in PubMed and Cochrane databases was conducted. RESULTS The risk of myocardial infarction was 0.3% in intermittent claudication, 1.2% in critical limb ischaemia and 1% in acute limb ischaemia. Corresponding risk of major stroke was 0.4%, 0.3% and 1.4%. Thrombolytic therapy was associated with a threefold risk of major stroke. Only a few studies relevant to the subject were found during the literature review. CONCLUSIONS In this population-based study we found a low risk of cardiac complications, but catheter-administered thrombolytic therapy entailed a non-negligible risk of major stroke.

Deep Femoral Vein Reconstruction of the Abdominal Aorta and Adaptation of the Neo-Aortoiliac System Bypass Technique in an Endovascular Era

Background: Primary infection of the abdominal aorta is a rare pathology that may threaten the integrity of the aortic wall, while secondary aortic prosthesis infection represents a devastating complication to open surgical and endovascular aortic surgery. Curative treatment is achievable by removal of all infected prosthetic material followed by a vascular reconstruction. Design and Methods: Twelve consecutive patients treated with the neo-aortoiliac system bypass (NAIS) procedure were reviewed. Nine were treated for a secondary aortic prosthesis infection (tube graft n = 3, bifurcated graft n = 4, endovascular aortic repair (EVAR) stent graft n = 1, and fenestrated EVAR [FEVAR] stent graft n = 1), while 3 patients underwent NAIS repair due to an emergent primary mycotic aortoiliac aneurysm. Primary Results: Ten of 12 patients survived 30 days. Three patients were operated on acutely, and 9 patients had elective or subacute NAIS surgery. Two of 3 patients operated acutely died within 30 days, whereas no 30-day or 1-year mortality was observed in patients undergoing elective or subacute surgery. The median time from primary reconstruction to the NAIS procedure was 11 months (range: 0-201 months). Stent grafts (n = 5 of 12) were in 4 cases explanted using endovascular balloon clamping. Of the explanted endografts, 2 patients presented with a secondary graft infection after EVAR/FEVAR, while 3 patients had been emergently treated with endovascular cuffs as a “bridge-to-surgery” procedure due to aortoenteric fistula (AEF). Patients who received a “bridge-to-surgery” regimen were treated with the NAIS procedure within 8 weeks (median 27 days, range: 27-60) after receiving emergency stent grafting. Principal Conclusions: Aortic balloon-clamping during explantation of infected aortic prosthetic endografts is feasible and facilitates complete endograft removal. Endovascular bridging procedures could be beneficiary in the treatment of AEF or anastomotic dehiscence due to graft infection, offering a possibility to convert the acute setting to an elective definitive reconstructive procedure with a higher overall success rate.