Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Repeat Rupture of a Giant Abdominal Aortic Aneurysm after EVAR

Introduction: Ruptured abdominal aortic aneurysms (AAAs) are known to be associated with high fatal outcomes. Giant AAAs are often defined as having a maximum diameter over 13 cm. Large AAAs over 8 cm have demonstrated a yearly rupture rate of 30–50%, which explains the rarity of giant AAAs. Endovascular repair of ruptured AAAs (rAAAs) is increasingly advocated because of the shorter hospital stay and fewer post-operative complications. Nonetheless, outcomes regarding mortality and cost-effectiveness show a large variability and long-term outcomes are lacking. Few data have been published on treatment of giant AAAs and rAAAs; however, open surgery is generally the preferred option. Report: An 83 year old presented to the Emergency Department with a history of ruptured abdominal aortic aneurysm treated with an aorto-uni-iliac endograft and a femorofemoral crossover bypass. During follow up, this was complicated by a symptomatic type III endoleak, which was treated by endovascular repair. During the current admission, he presented with a re-rupture of his former aneurysm, which now was 18 cm diameter because of a type IA endoleak. Open surgical repair was performed and the post-operative course was without complications. Discussion: The current case underlines the value of vascular surgeons being able to perform both open and endovascular surgery in rAAA. Keywords: Giant abdominal aorta aneurysm, Re-rupture, Endoleak, EVAR, Open repai

Identifying high risk for proximal endograft failure after endovascular aneurysm repair in patients suitable for both open and endovascular elective aneurysm repair

Objective: Proximal endograft failure (type Ia endoleak or migration) after endovascular aneurysm repair (EVAR) is associated with hostile aneurysm neck morphology. Neck scoring systems were developed to predict proximal endograft failure but were studied in retrospective studies, which, due to selection bias, may have led to an overestimation of bad outcomes after EVAR. To predict patients who benefit from open repair, preoperative neck morphology and occurrence of long-term proximal endograft failure were investigated in patients enrolled in the endovascular arm of the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial who were suitable for open repair by definition and have long-term follow-up. Methods: A post-hoc on-treatment analysis of patients after EVAR was performed in 171 patients. Aneurysm neck morphology was quantified using the aneurysm severity grading (ASG) neck score calculated on preoperative computed tomography angiography images. The ASG neck score was used to predict proximal endograft failure. Receiver operating characteristic analysis was performed to calculate a threshold to divide favorable and unfavorable aneurysm necks (low and high risk); positive and negative likelihood-ratios were calculated accordingly. Freedom from proximal endograft failure was compared between groups using Kaplan-Meier analysis. Results: During a median follow-up of 7.6 years, 20 patients suffered proximal endograft failure. Receiver operating characteristic analysis showed an area under the curve of 0.77 (95% confidence interval [CI], 0.65-0.90; P <.001), indicating acceptable prediction. The threshold was determined at ASG neck score ≥5; 30 patients had unfavorable neck morphology, of whom 11 developed proximal endograft failure. The positive likelihood-ratio was 4.4 (95% CI, 2.5-7.8), and the negative likelihood-ratio was 0.51 (95% CI, 0.3-0.8). Twelve years postoperatively, freedom from proximal endograft failure was 91.7% in the favorable group and 53.2% in the unfavorable group, a difference of 38.5% (95% CI, 13.9-63.1; P <.001). Conclusions: In this study, the ASG neck score predicted proximal endograft failure during the entire follow-up. This exhibits the persistent risk for proximal endograft failure long after EVAR and calls for ongoing surveillance especially in patients with unfavorable aneurysm necks

Repeat Rupture of a Giant Abdominal Aortic Aneurysm after EVAR

Introduction: Ruptured abdominal aortic aneurysms (AAAs) are known to be associated with high fatal outcomes. Giant AAAs are often defined as having a maximum diameter over 13 cm. Large AAAs over 8 cm have demonstrated a yearly rupture rate of 30–50%, which explains the rarity of giant AAAs. Endovascular repair of ruptured AAAs (rAAAs) is increasingly advocated because of the shorter hospital stay and fewer post-operative complications. Nonetheless, outcomes regarding mortality and cost-effectiveness show a large variability and long-term outcomes are lacking. Few data have been published on treatment of giant AAAs and rAAAs; however, open surgery is generally the preferred option. Report: An 83 year old presented to the Emergency Department with a history of ruptured abdominal aortic aneurysm treated with an aorto-uni-iliac endograft and a femorofemoral crossover bypass. During follow up, this was complicated by a symptomatic type III endoleak, which was treated by endovascular repair. During the current admission, he presented with a re-rupture of his former aneurysm, which now was 18 cm diameter because of a type IA endoleak. Open surgical repair was performed and the post-operative course was without complications. Discussion: The current case underlines the value of vascular surgeons being able to perform both open and endovascular surgery in rAAA

Systematic review of embolization of type I endoleaks using liquid embolic agents

Objective: The long-term success of endovascular aneurysm repair (EVAR) is limited by complications, most importantly endoleaks. In case of (persistent) type I endoleak (T1EL), secondary intervention is indicated to prevent secondary aneurysm rupture. Different treatment options are suggested for T1ELs, such as endo anchors, (fenestrated) cuffs, embolization, or open conversion. Currently, the treatment of T1EL with liquid embolic agents is available; however, results are not yet addressed. This review presents the safety and efficacy of embolization with liquid embolic agents for treatment of T1ELs after EVAR. Methods: A systematic literature search was performed for all studies reporting the use of liquid embolic agents as monotherapy for treatment of T1ELs after EVAR. Patient numbers, technical success (successful delivery of liquid embolics in the T1EL) and clinical success (absence of aneurysm related death, endoleak recurrence or additional interventions during follow-up) were examined. Results: Of 1604 articles, 10 studies met the selection criteria, including 194 patients treated with liquid embolics; 73.2% of the patients were male with a median age of 71 years. The overall technical success was 97.9%. Clinical success was 87.6%. Because the median follow-up was only 13.0 months (range, 1-89 months), data on long-term success are almost absent. Four cases (2.1%) of secondary aneurysm rupture after embolization owing to endoleak recurrence were reported. All ruptures occurred in aneurysms exceeding initial treatment diameter of 70 mm. Conclusions: Initial technical success after liquid embolization for T1EL is high, although long-term clinical success rates are lacking. Within this review, the risk of secondary rupture is comparable with untreated T1EL at 2% with a median follow-up of 13 months, regardless of the initial success of embolization. In general, no decrease in secondary aneurysm rupture after embolization of T1EL after EVAR is demonstrated, although the results of late embolization are debated

What we have learned from in-vitro studies of the chimney endovascular technique for treatment of complex abdominal aortic aneurysms: A systematic review

Background: A considerable number of patients with abdominal aortic aneurysms (AAA) is not eligible for standard endovascular repair. These complex cases require alternative surgical approaches including the readily available chimney graft endovascular aneurysm repair (Ch-EVAR) or sealing (Ch-EVAS). The optimal configuration for Ch-EVAR or Ch-EVAS is important for success but not yet known. Objective: The aim of the present study was to analyze current data of the outcomes of in-vitro chimney graft treatment in complex AAA. Methods: A systematic review following PRISMA guidelines was conducted including studies reporting on gutter size, main graft compression, and chimney graft compression in in-vitro configurations. Results: The search resulted in 285 articles. 11 studies considering 219 individual tests could be included. Gutter size was comparable between Ch-EVAR and Ch-EVAS configurations. In Ch-EVAR set-ups, the deployed BECG were Advanta V12, VIABAHN®, and BeGraft. One type of SECG was used: VIABAHN®. The four types of main grafts (MG) deployed were: Endurant™ I/II; EXCLUDER Conformable AAA Endoprosthesis and AAA Endoprosthesis, and AFX™ Endovascular AAA Delivery System. In the EVAS-configurations, the Nellix® EVAS system was deployed. In general, SECG presented smaller gutters with higher chimney graft compression. 30% main grafts oversizing seems to give the smallest gutters without high risk of infolding of MG. Oversizing, EndoAnchors, and secondary endobag filling (in Ch-EVAS) reduced gutter sizes. CG ballooning during the entire polymer injection in Ch-EVAS prevented CG compression. Conclusion: In-vitro investigations provide insight in optimal Ch-EVAR and Ch-EVAS configurations for simulated complex AAA repair. The findings above might aid physicians in their planning to potential CG set-ups and can be used in future research to refine the most optimal configuration for chimney graft technique in complex AAA

Cold Renal Perfusion During Simulation of Juxtarenal Aortic Aneurysm Repair Reduces Systemic Oxidative Stress and Sigmoid Damage in Rats

Objectives: Juxtarenal aortic surgery induces renal ischaemia reperfusion, which contributes to systemic inflammatory tissue injury and remote organ damage. Renal cooling during suprarenal cross clamping has been shown to reduce renal damage. It is hypothesised that renal cooling during suprarenal cross clamping also has systemic effects and could decrease damage to other organs, like the sigmoid colon. Methods: Open juxtarenal aortic aneurysm repair was simulated in 28 male Wistar rats with suprarenal cross clamping for 45 min, followed by 20 min of infrarenal aortic clamping. Four groups were created: sham, no, warm (37 °C saline), and cold (4 °C saline) renal perfusion during suprarenal cross clamping. Primary outcomes were renal damage and sigmoid damage. To assess renal damage, procedure completion serum creatinine rises were measured. Peri-operative microcirculatory flow ratios were determined in the sigmoid using laser Doppler flux. Semi-quantitative immunofluorescence microscopy was used to measure alterations in systemic inflammation parameters, including reactive oxygen species (ROS) production in circulating leukocytes and leukocyte infiltration in the sigmoid. Sigmoid damage was assessed using digestive enzyme (intestinal fatty acid binding protein - I-FABP) leakage, a marker of intestinal integrity. Results: Suprarenal cross clamping caused deterioration of all systemic parameters. Only cold renal perfusion protected against serum creatinine rise: 0.45 mg/dL without renal perfusion, 0.33 mg/dL, and 0.14 mg/dL (p = .009) with warm and cold perfusion, respectively. Microcirculation in the sigmoid was attenuated with warm (p = .002) and cold renal perfusion (p = .002). A smaller increase of ROS production (p = .034) was seen only after cold perfusion, while leukocyte infiltration in the sigmoid colon decreased after warm (p = .006) and cold perfusion (p = .018). Finally, digestive enzyme leakage increased more without (1.5AU) than with warm (1.3AU; p = .007) and cold renal perfusion (1.2AU; p = .002). Conclusions: Renal ischaemia/reperfusion injury after suprarenal cross clamping decreased microcirculatory flow, increased systemic ROS production, leukocyte infiltration, and I-FABP leakage in the sigmoid colon. Cold renal perfusion was superior to warm perfusion and reduced renal damage and had beneficial systemic effects, reducing sigmoid damage in this experimental study

Gutter Characteristics and Stent Compression of Self-Expanding vs Balloon-Expandable Chimney Grafts in Juxtarenal Aneurysms Models

Purpose: To assess in silicone juxtarenal aneurysm models the gutter characteristics and compression of different types of chimney graft (CG) configurations. Materials and Methods: Fifty-seven combinations of Excluder C3 or Conformable Excluder stent-grafts (23, 26, and 28.5 mm) were deployed in 2 silicone juxtarenal aneurysm models with 3 types of CGs: Viabahn self-expanding (VSE; 6 and 13 mm) or Viabahn balloon-expandable (VBX; 6, 10, and 12 mm) stent-grafts and Advanta V12 balloon-expandable stent-grafts (ABX; 6 and 12 mm). Setups were divided into 4 groups on the basis of increasing CG and main graft (MG) diameters. Two independent observers assessed gutter size and type as well as CG compression on computed tomography scans using postprocessing software. Results: In the smaller diameter combinations (6-mm CG and 23-, 26-, and 28.5-mm MGs), both VSE (p=0.006 to 0.050) and ABX (p=0.045 to 0.050) showed lower gutter areas and volumes compared with VBX. In turn, the VBX showed a nonsignificant tendency to decreased compression, especially compared to ABX. Use of the Excluder C3 showed a 6-fold increase in type A1 gutters (related to type Ia endoleak) as compared to the Conformable Excluder (p=0.018). Balloon-expandable stent-grafts (both ABX and VBX) showed a 3-fold increase in type A1 gutters in comparison with self-expanding stent-grafts (p=0.008). Conclusion: The current study suggests that use of the Conformable Excluder in combination with VSE chimney grafts is superior to the other tested CG/MG combinations in terms of gutter size, gutter type, and CG compression

The Value of Sigmoidoscopy to Detect Colonic Ischaemia After Ruptured Abdominal Aortic Aneurysm Repair

Objectives: Diagnosing colonic ischaemia (CI) after ruptured abdominal aortic aneurysm (RAAA) repair is challenging. This study determined the diagnostic value of sigmoidoscopy in patients suspected of CI after RAAA repair. Methods: This was a retrospective multicentre cohort study. Patients who underwent RAAA repair in three hospitals in Amsterdam, the Netherlands, between 2004 and 2011 (AJAX cohort) were included. Sigmoidoscopies were carried out based on clinical judgment. Endoscopy results were classified as “no ischaemia,” “mild CI,” or “moderate to severe CI.” The surgical diagnosis was classified as “transmural” or “no transmural” CI. The value of sigmoidoscopy was assessed with calculation of positive and negative predictive values (PPV, NPV) with 95% CI for transmural CI. Logistic regression analysis was used to express the association of risk factors with CI as adjusted OR. Results: Transmural CI was diagnosed in 23 of 351 patients (6.6%). Thirteen of sixteen patients (81%) who underwent direct laparotomy for high suspicion of CI indeed had transmural CI. Forty-six patients (13%) underwent sigmoidoscopy. The prevalence of transmural CI was 22% (10/46; 95% CI 12–36%) in these patients. The PPV for transmural CI of “moderate to severe CI” on sigmoidoscopy was 73% (8/11; 95% CI 43–90%). The PPV of “mild CI” on sigmoidoscopy was 11% (2/19; 95% CI 2.9–31%). The NPV of “no ischaemia” on sigmoidoscopy was 100% (95% CI 78–100%). Cardiac comorbidity (OR 3.1, 95% CI 1.19–7.97), low first haemoglobin (OR 0.6, 95% CI 0.47–0.87), and high vasopressor administration (OR 9.4, 95% CI 1.99–44.46) were independently associated with CI. Conclusions: Sigmoidoscopy increases the likelihood of correctly identifying the presence or absence of transmural CI, especially in patients with a moderate clinical suspicion for CI after RAAA repair

Gutter Characteristics and Stent Compression of Self-Expanding vs Balloon-Expandable Chimney Grafts in Juxtarenal Aneurysm Models

Purpose: To assess in silicone juxtarenal aneurysm models the gutter characteristics and compression of different types of chimney graft (CG) configurations. Materials and Methods: Fifty-seven combinations of Excluder C3 or Conformable Excluder stent-grafts (23, 26, and 28.5 mm) were deployed in 2 silicone juxtarenal aneurysm models with 3 types of CGs: Viabahn self-expanding (VSE; 6 and 13 mm) or Viabahn balloon-expandable (VBX; 6, 10, and 12 mm) stent-grafts and Advanta V12 balloon-expandable stent-grafts (ABX; 6 and 12 mm). Setups were divided into 4 groups on the basis of increasing CG and main graft (MG) diameters. Two independent observers assessed gutter size and type as well as CG compression on computed tomography scans using postprocessing software. Results: In the smaller diameter combinations (6-mm CG and 23-, 26-, and 28.5-mm MGs), both VSE (p=0.006 to 0.050) and ABX (p=0.045 to 0.050) showed lower gutter areas and volumes compared with VBX. In turn, the VBX showed a nonsignificant tendency to decreased compression, especially compared to ABX. Use of the Excluder C3 showed a 6-fold increase in type A1 gutters (related to type Ia endoleak) as compared to the Conformable Excluder (p=0.018). Balloon-expandable stent-grafts (both ABX and VBX) showed a 3-fold increase in type A1 gutters in comparison with self-expanding stent-grafts (p=0.008). Conclusion: The current study suggests that use of the Conformable Excluder in combination with VSE chimney grafts is superior to the other tested CG/MG combinations in terms of gutter size, gutter type, and CG compression