Sex differences in outcomes after revascularization for acute lower limb ischemia: Propensity score adjusted analysis.

BACKGROUND: Previous reports have suggested higher rates of mortality and amputation for female patients in acute lower limb ischemia (ALI). The aims of the present study were to investigate if there is a difference in mortality, amputation, and fasciotomy between the sexes. METHODS: A retrospective cohort study of consecutive patients undergoing index revascularization for ALI between 2001 and 2018 was conducted. A propensity score was created through a logistic regression with female/male sex as an outcome. Cox regression analyses for 90-day and 1-year mortality, combining major amputation/mortality, and logistic regression for major bleeding and fasciotomy, were performed. All analyses were performed with and without adjusting for propensity score. RESULTS: A total of 709 patients were included in the study of which 45.9% were women. Mean age was 72.1 years. Females were older and had higher rates of atrial fibrillation, embolic disease, and lower estimated glomerular filtration rate, while men more often had anemia and chronic peripheral arterial disease. Mortality at 1 year was 21.2% for women and 14.7% for men. The adjusted hazard ratio for 1-year mortality was 0.99 (95% CI 0.67-1.46). Fasciotomy was performed in 7.1% of female and 12.8% of male patients; the adjusted odds ratio was 0.52 (95% CI 0.29-0.91). CONCLUSION: Sex was not found to be an independent risk factor for mortality or combined major amputation/mortality after revascularization for acute lower limb ischemia, whereas women had lower odds of undergoing fasciotomy. Whether women are underdiagnosed or do not develop acute compartment syndrome in the lower leg as often as men should be evaluated prospectively.

Multicenter parallel randomized trial evaluating incisional negative pressure wound therapy for the prevention of surgical site infection after lower extremity bypass.

OBJECTIVE: Incisional negative pressure wound therapy (iNPWT) applied over all incisions after lower extremity bypass in the prevention of surgical site infections (SSIs) is unclear. The primary and secondary aims of this study were to investigate if prophylactic iNPWT after the elective lower extremity bypass prevents SSI and other surgical wound complications. METHODS: This was a multicenter, parallel, randomized controlled trial. Patients undergoing elective lower extremity bypass in 3 hospitals were randomized to either iNPWT or standard dressings. SSIs or other wound complications were assessed within the first 90 days by wound care professionals blinded to the randomized result. The validated Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues, Isolation of bacteria, and Stay (ASEPSIS) score was used to objectively assess the wounds. ASEPSIS score ≥21 is defined as an SSI. Unilateral and bilateral groups were analyzed with the Fisher exact test and the McNemar test, respectively. RESULTS: In the unilateral group (n = 100), the incidence of SSI in the iNPWT group was 34.9% (15/43), compared with 40.3% (23/57) in the control group, according to the ASEPSIS score (P = .678). In the bilateral group (n = 7), the SSI rate was 14.3% (1/7) in the iNPWT group compared with 14.3% (1/7) in the control group (P = 1.00). In the unilateral group, there was a higher wound dehiscence rate in the control group (43.9%) compared with the iNPWT group (23.3%) (P = .0366). No serious iNPWT-related adverse events were recorded. CONCLUSIONS: There was no reduction of SSI rates in leg incisions with iNPWT compared with standard dressings in patients undergoing elective lower extremity bypass, whereas iNPWT reduced the incidence of wound dehiscence.

Outcomes After Endovascular Aortic Intervention in Patients With Connective Tissue Disease.

Importance: Endovascular treatment is not recommended for aortic pathologies in patients with connective tissue diseases (CTDs) other than in redo operations and as bridging procedures in emergencies. However, recent developments in endovascular technology may challenge this dogma. Objective: To assess the midterm outcomes of endovascular aortic repair in patients with CTD. Design, Setting, and Participants: For this descriptive retrospective study, data on demographics, interventions, and short-term and midterm outcomes were collected from 18 aortic centers in Europe, Asia, North America, and New Zealand. Patients with CTD who had undergone endovascular aortic repair from 2005 to 2020 were included. Data were analyzed from December 2021 to November 2022. Exposure: All principal endovascular aortic repairs, including redo surgery and complex repairs of the aortic arch and visceral aorta. Main Outcomes and Measures: Short-term and midterm survival, rates of secondary procedures, and conversion to open repair. Results: In total, 171 patients were included: 142 with Marfan syndrome, 17 with Loeys-Dietz syndrome, and 12 with vascular Ehlers-Danlos syndrome (vEDS). Median (IQR) age was 49.9 years (37.9-59.0), and 107 patients (62.6%) were male. One hundred fifty-two (88.9%) were treated for aortic dissections and 19 (11.1%) for degenerative aneurysms. One hundred thirty-six patients (79.5%) had undergone open aortic surgery before the index endovascular repair. In 74 patients (43.3%), arch and/or visceral branches were included in the repair. Primary technical success was achieved in 168 patients (98.2%), and 30-day mortality was 2.9% (5 patients). Survival at 1 and 5 years was 96.2% and 80.6% for Marfan syndrome, 93.8% and 85.2% for Loeys-Dietz syndrome, and 75.0% and 43.8% for vEDS, respectively. After a median (IQR) follow-up of 4.7 years (1.9-9.2), 91 patients (53.2%) had undergone secondary procedures, of which 14 (8.2%) were open conversions. Conclusions and Relevance: This study found that endovascular aortic interventions, including redo procedures and complex repairs of the aortic arch and visceral aorta, in patients with CTD had a high rate of early technical success, low perioperative mortality, and a midterm survival rate comparable with reports of open aortic surgery in patients with CTD. The rate of secondary procedures was high, but few patients required conversion to open repair. Improvements in devices and techniques, as well as ongoing follow-up, may result in endovascular treatment for patients with CTD being included in guideline recommendations.

Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms.

OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs). METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM). RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively. CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.

Infective popliteal artery aneurysm by Streptococcus equi: An unusual pathogen.

We report the case of a 63-year-old man who presented with a 2-week complaint of lower extremity pain, swelling, and low-grade fever after an episode of septic arthritis in the ipsilateral knee. The investigation showed a rapidly expanding popliteal artery aneurysm (PAA). The rare clinical entity of an infective PAA was suspected and was confirmed by the cultures obtained at the right femoropopliteal bypass with an autologous vein graft and subtotal resection of the aneurysm sac. Streptococcus equi was identified as the primary pathogen, which, to the best of our knowledge, has not been previously described for an infective PAA.

Short-Term Complications and Outcomes in Pharmaco-Mechanical Thrombolysis First and Catheter-Directed Thrombolysis First in Patients with Acute Lower Limb Ischemia.

BACKGROUND: Pharmaco-mechanical thrombolysis (PMT) has emerged as a treatment option in patients with acute lower limb ischemia (ALI), especially Rutherford IIb (motor deficit) for rapid revascularization, but supportive data is scarce. The aim of the present study was to compare the effects of thrombolysis, complications, and outcomes of PMT first versus catheter-directed thrombolysis (CDT) first in a large cohort of patients with ALI. METHODS: All endovascular thrombolytic/thrombectomy events in patients with ALI performed between January 1st, 2009, and December 31st, 2018 (n = 347) were included. Successful thrombolysis/thrombectomy was defined as complete or partial lysis. Reasons for using PMT were described. Complications such as major bleeding, distal embolization, and new onset of renal impairment, and major amputation and mortality at 30 days were compared between PMT (AngioJet) first and CDT first groups in a multivariable logistic regression model with adjustment for age, gender, atrial fibrillation, and Rutherford IIb. RESULTS: The most common reason for initial use of PMT was the need for rapid revascularization, and the most common reason for use of PMT after CDT was the insufficient effect of CDT. Presentation of Rutherford IIb ALI was more common in the PMT first group (36.2% vs. 22.5%, respectively, P = 0.027). Among the 58 patients receiving PMT first, 36 (62.1%) were terminated within a single session of therapy without need of CDT. The median duration of thrombolysis was shorter (P < 0.001) for the PMT first group (n = 58) compared to the CDT first group (n = 289) (4.0 hr vs. 23.0 hr, respectively). There was no significant difference in amount of tissue plasminogen activator given, successful thrombolysis/thrombectomy (86.2% and 84.8%), major bleeding (15.5% and 18.7%), distal embolization (25.9% and 16.6%), major amputation or mortality at 30-days (13.8% and 7.7%) in the PMT first compared to the CDT first group, respectively. The proportion of new onset of renal impairment was higher in the PMT first compared to the CDT first group (10.3% vs. 3.8%, respectively), and the increased odds (odds ratio 3.57, 95% confidence interval 1.22-10.41) were maintained in the adjusted model. In Rutherford IIb ALI, no difference in rate of successful thrombolysis/thrombectomy (76.2% and 73.8%), complications or 30-day outcomes was found between PMT first (n = 21) and CDT (n = 65) first group. CONCLUSIONS: PMT first appears to be a good treatment alternative to CDT in patients with ALI, including Rutherford IIb. The found renal function deterioration in the PMT first group needs to be evaluated in a prospective, preferably randomized trial.

Prophylactic and Therapeutic Fasciotomy for Acute Compartment Syndrome after Revascularization for Acute Lower Limb Ischemia-Renal and Wound Outcomes.

BACKGROUND: Acute Compartment Syndrome (ACS) is a significant complication after revascularization for acute lower limb ischemia (ALI). High risk patients sometimes undergo prophylactic fasciotomy (PF) to prevent ACS. Patients that develop ACS undergo therapeutic fasciotomy (TF). The optimal timing of fasciotomy has been debated. The aim of this study was to describe and compare renal and wound outcomes in patients undergoing PF and TF. METHODS: A retrospective cohort study including 76 patients undergoing PF (n = 40) or TF (n = 36) after revascularization for ALI between 2006 and 2018. Estimated glomerular filtration rate (e-GFR) was used to evaluate renal function and compare within (paired-samples t-test) and between (analysis of variance) groups. Wound complications and healing time were compiled from the complete wound healing period and compared between groups with Pearson's chi-squared-and log-rank test, respectively. RESULTS: E-GFR improved over the in-hospital period with 8.2 ml/min/1.73 m2 (95% confidence interval [CI] 2.4-14.1, P = 0.007) in the PF group and 4.4 ml/min/1.73 m2 (95% CI 1.2-7.7, P = 0.010) in the TF group, with no significant difference between the 2 groups (0.3 ml/min/1.73 m2, 95% CI -6.7 to 7.4, P = 0.93). The wound infection rate was higher after TF (PF = 60.6 % and TF = 82.4 %, P = 0.048), whereas rate of other wound complications (PF = 61.3 % and TF = 35.3%, P = 0.036) was higher after PF. CONCLUSIONS: Overall wound complications were high, whereas renal function improved during in-hospital stay. A more conservative approach to fasciotomy could avoid unnecessary fasciotomies and reduce wound complications, while holding the potential to sufficiently preserve renal function if fasciotomy is needed for ACS. This would be possible and safe if an early diagnosis and treatment of ACS can be ensured.

Contrast-Associated Acute Kidney Injury in Patients with and without Diabetes Mellitus Undergoing Computed Tomography Angiography and Local Thrombolysis for Acute Lower Limb Ischemia.

PurposeRepetitive iodinated contrast media exposure may be harmful for the kidneys. The aim of the present study was to evaluate if patients with diabetes mellitus (DM) undergoing CT angiography (CTA) and local continuous thrombolysis for acute lower limb ischemia (ALI) had an increased risk of developing contrast-associated acute kidney injury (CA-AKI) compared to patients without DM. Methods: This is a retrospective study of patients undergoing CTA and local continuous thrombolysis due to ALI between 2001 and 2018. CA-AKI was defined as a 25% increase in serum creatinine within 72 hours after latest contrast administration. Results: There was no difference (P = .30) in the frequency of CA-AKI between patients with (27.9%; n = 43) and without DM (20.6%; n = 170). Among patients with CA-AKI, patients with DM had a lower (P < .001) estimated glomerular filtration rate (eGFR) at discharge (55 ml/min/1.73 m2) than at admission (70 ml/min/1.73 m2), while no such difference was found in the group without DM (P = .20). The gram-iodine dose/eGFR ratio was higher (P < .001) in patients with CA-AKI (median 1.49, [IQR 1.34-1.81]) than in those who did not develop CA-AKI (median 1.05 [IQR 1.00-1.13]). There was a trend that gram-iodine dose/eGFR ratio (OR 1.42/standard deviation increment, 95% CI 1.00-2.02; P = .050) was associated with an increased risk of CA-AKI, after adjusting for DM, age, and gender. Conclusions: The frequency of CA-AKI was high after CTA and local continuous thrombolysis for ALI without shown increased frequency for the DM group. Among patients with CA-AKI, however, patients with DM had worse renal function at discharge than those without DM. The gram-iodine dose/eGFR ratio in these patients needs to be lower to improve renal outcomes, particularly in patients with DM.

Influence of diabetes on diagnostic performance of computed tomography angiography of the calf arteries in acute limb ischemia.

BACKGROUND: Patients with diabetes mellitus (DM) have a more extensive distal arterial occlusive disease compared to non-diabetic patients. Diagnostic imaging is a necessity to identify the location and extent of the arterial occlusion in acute limb ischemia (ALI). Computed tomography angiography (CTA) is the most commonly used modality and the diagnostic performance with CTA of calf arteries may be questioned. PURPOSE: To evaluate diagnostic performance of CTA of calf arteries in ALI and to compare patients with and without DM. MATERIAL AND METHODS: All thrombolytic treatments performed during 2001-2018 in patients with ALI were included. Initial digital subtraction angiography (DSA) and CTA of all patients were classified according to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) below-the-knee arteries and compared to CTA. Two raters assessed the CTA images independently. Inter-rater reliability was expressed as intraclass correlation (ICC) with 95% confidence intervals (CI). RESULTS: Patients with (n = 23) and without (n = 85) DM had lower (P = 0.006) glomerular filtration rate. ICC between CTA and DSA was 0.33 (95% CI -0.22 to 0.56) and 0.71 (95% CI 0.38-0.68) in patients with and without DM, respectively. Sensitivity with CTA for TASC D lesions in patients with and without DM was 0.14 (95% CI -0.12 to 0.40) and 0.64 (95% CI 0.48-0.80), respectively. CONCLUSION: The sensitivity of CTA for assessment of infra-popliteal TASC D lesions in patients with ALI was not acceptable in patients with DM in contrast to those without DM. Another imaging option at present times should be considered for patients with DM.

Amputation-free survival in patients with diabetic foot ulcer and peripheral arterial disease: Endovascular versus open surgery in a propensity score adjusted analysis.

AIMS: The aim of the present study was to compare outcomes of endovascular surgery versus open vascular surgery in patients with diabetic foot ulcer (DFU) and peripheral arterial disease (PAD). METHODS: Between 1984 and 2006, 1151 patients with DFU were admitted to the diabetic foot care team. Three hundred seventy-six patients with 408 limbs were consecutively included at a multidisciplinary foot center, 289 limbs were treated with endovascular surgery and 119 limbs with open vascular surgery first strategy. A propensity score adjusted analysis was performed to compare outcomes for type of revascularization. RESULTS: Major amputation rates at 3 years were 17.0% and 16.8% (p = 0.97) and mortality at 3 years were 43.1% and 46.5% (p = 0.55) after endovascular surgery and open vascular surgery, respectively. In the propensity score adjusted analysis, patients undergoing endovascular surgery first had similar outcomes in terms of major amputation, mortality, combined major amputation/mortality compared to those undergoing open vascular surgery. Longer time to intervention (p = 0.003) was associated with increased major amputation rate in the multivariable Cox regression analysis. CONCLUSION: The endovascular surgery first and open vascular surgery first strategies were associated with similar long-term results in a large cohort of patients with DFU and PAD undergoing revascularization. Rapid revascularization reduces the risk of amputation.

Proposed Classification of Incision Complications: Analysis of a Prospective Study on Elective Open Lower-Limb Revascularization.

Background: Incision complications (IC) have a significant impact on procedure-related morbidity after lower-limb revascularization. One of the most studied IC is surgical site infection (SSI). Reporting these complications in a uniform way is crucial to evaluate treatment approaches. The aim of this study was to propose a comprehensive classification of IC and apply it to compare SSI with other IC in a trial on elective open lower-limb revascularization procedures. Methods: Two hundred twenty-three eligible patients undergoing elective unilateral inguinal and infra-inguinal arterial vascular surgery were extracted from a randomized controlled trial on incisional negative-pressure wound therapy (NPWT) on inguinal vascular surgical incisions. The IC were classified by grades of severity (grade 0-6) that focused on IC-related consequences such as out-patient treatment (grade 1), prolonged in-patient treatment (grade 2), re-admission (grade 3), and re-operation (grade ≥4). An SSI was defined by the ASEPSIS score criteria. Results: An SSI was diagnosed in 63 patients (28.3%). Thirty-five of 160 patients (21.8%) not suffering from SSI underwent IC treatment. Treatment for IC was recorded for 25/144 patients (17.4%) with satisfactory site healing as judged by the ASEPSIS score. The median incision-related in-hospital stay in those with SSI (n = 79) and disturbed healing (n = 16) according to the ASEPSIS score was 13 days in both groups (p = 0.53). Five patients had peri-vascular SSI (IC grade 4 n = 4; grade 5 n = 1). The proposed classification of IC and the ASEPSIS score correlated highly (r = 0.77; p < 0.001). Inter-rater reliability for IC grading was substantial for three investigators with different levels of experience (k = 0.81, 0.71, and 0.70). Conclusions: The proposed incision classification suggests a comparable clinical significance of vascular IC in terms of IC-related in-patient stay, whether there was a surgical site infection or not. This classification system requires external validation.

Amputation-Free Survival in Patients With Diabetes Mellitus and Peripheral Arterial Disease With Heel Ulcer: Open Versus Endovascular Surgery.

BACKGROUND:: Heel ulcers in patients with diabetes mellitus (DM) and peripheral arterial disease (PAD) are hard to heal. The aim of the present study was to evaluate the difference in amputation-free survival (AFS) between open and endovascular revascularization in patients with DM, PAD, and heel ulcers. METHODS:: Retrospective comparative study of results of open versus endovascular surgery in patients with DM, PAD, and heel ulcer presented at the multidisciplinary diabetes foot clinic between 1983 and 2013. RESULTS:: Patients with heel ulcers were treated with endovascular intervention (n = 97) and open vascular surgery (n = 30). Kaplan-Meier analysis showed that the AFS was higher in patients undergoing open vascular surgery compared to the endovascular group ( P = .009). Multivariate analysis showed that open vascular surgery versus endovascular therapy (hazard ratio 2.1, 95% confidence interval 1.1-3.9; P = .025) was an independent factor associated with higher AFS. The proportion of patients undergoing endovascular therapy in the former (1983-2000) time period was 47% compared to 89% in the latter (2001-2013) time period ( P < .001). CONCLUSION:: The AFS was higher after open than endovascular surgery among patients with DM and PAD with heel ulcer. These results suggest that open vascular surgery should be offered more often as opposed to current practice.

Outcome of intra-arterial thrombolysis in patients with diabetes and acute lower limb ischemia: a propensity score adjusted analysis.

The presence of diabetes mellitus is rarely addressed in acute lower limb ischaemia (ALLI). The aim of this study was to evaluate the outcome of local intra-arterial thrombolysis for ALLI in patients with diabetes mellitus (DM). Outcome of all thrombolytic events performed in an endovascular first-strategy centre during a 13-year period between 2001 and 2013 in patients with ALLI were followed to January 2017. A propensity score adjusted analysis was performed to evaluate results in patients with (n = 83) versus without (n = 316) DM. Patients with DM were younger (p = 0.001), more often women (p = 0.014), more often had renal insufficiency (p = 0.041), foot ulcers (p < 0.001), and thrombosis (p = 0.032) than the patients without DM. At presentation, patients with DM had a lower degree of ischemia judged by the Rutherford classification, compared to those without DM (p = 0.023). None of the 83 diabetic patients had a popliteal artery aneurysm, compared to 25 (7.9%) of the 316 patients without DM (p = 0.008). The amount of tPA administered to patients with DM was higher than to patients without DM (p = 0.03). In the propensity score adjusted analysis, patients with DM had a higher rate of major amputation at 1 (OR 2.52; 95% CI 1.22-5.20) and 3 years (OR 2.52; 95% CI 1.26-5.04), and a lower amputation-free survival at 3 years (OR 0.46; 95% CI 0.25-0.85), than those without DM. Patients with DM presenting with ALLI differ in clinical characteristics, presentation, and aetiology compared to patients with DM, and have a higher rate of major amputation and lower amputation-free survival rate after intra-arterial thrombolysis.

Apolipoproteins, lipids and risk of cancer.

The epidemiological evidence for an obesity-cancer association is solid, whereas the association between obesity-associated lipoprotein levels and cancer is less evident. We investigated circulating levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) and association to risk of overall cancer and common cancer forms. The Malmö Diet and Cancer Study, a population-based prospective cohort study, enrolled 17,035 women and 11,063 men (1991-1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow-up, January 1, 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort and HDL-C and LDL-C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HRadj ApoA1 = 0.98, 95%CI: 0.95,1.01; HRadj ApoB = 1.01, 95%CI: 0.98-1.04). Among men, ApoB was positively associated with cancer risk (HRadj ApoB = 1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HRadj = 0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HRadj = 0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HRadj = 1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HRadj = 1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer.

The target for statins, HMG-CoA reductase, is expressed in ductal carcinoma-in situ and may predict patient response to radiotherapy.

BACKGROUND: Patients with ductal carcinoma-in-situ (DCIS) are currently not prescribed adjuvant systemic treatment after surgery and radiotherapy. Prediction of DCIS patients who would benefit from radiotherapy is warranted. Statins have been suggested to exert radio-sensitizing effects. The target for cholesterol-lowering statins is HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway. The aim of this study was to examine HMGCR expression in DCIS and study its treatment predictive value. METHODS: A population-based cohort including 458 women diagnosed with primary DCIS between 1986 and 2004 were followed until November 2011 to study long-term survival. Tumor tissue microarrays were constructed, and immunohistochemical analyses were performed to detect cytoplasmic protein expression of HMGCR. The association between DCIS HMGCR expression and invasive breast cancer recurrence-free survival (RFSinv) and overall survival (OS) was analyzed by Kaplan-Meier curves, log rank test, and Cox proportional hazard analysis. RESULTS: HMGCR was strongly expressed in 24 % of the assessed DCIS samples, moderately expressed in 46 %, and weakly expressed in 23 %; no expression was detected in 7 % of the samples. During the follow-up time (median 13.8 years), 61 patients were diagnosed with an invasive breast cancer recurrence, and 80 patients died. A crude analysis showed no survival benefit from radiotherapy. However, patients with strong HMGCR expression showed an improved RFSinv (log rank, p = 0.03) and OS (log rank, p = 0.04) after radiotherapy. No statistically significant interaction was observed for HMGCR and radiotherapy (RFSinv p = 0.69 and OS p = 0.29). CONCLUSIONS: This study demonstrates HMGCR expression in DCIS and suggests HMGCR as a predictive marker of response to postoperative radiotherapy in DCIS, although the test for interaction was nonsignificant. Future DCIS studies addressing the potential of statin treatment targeting HMGCR are warranted.