Franziska Heidemann

Selectins Mediate Small Cell Lung Cancer Systemic Metastasis

Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC) patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181). However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

Registry and health insurance claims data in vascular research and quality improvement

The expansion of procedures in multidisciplinary vascular medicine has sparked a controversy regarding measures of quality improvement. In addition to primary registries, the use of health insurance claims data is becoming of increasing importance. However, due to the fact that health insurance claims data are not collected for scientific evaluation but rather for reimbursement purposes, meticulous validation is necessary before and during usage in research and quality improvement matters. This review highlights the advantages and disadvantages of such data sources. A recent comprehensive expert opinion panel examined the use of health insurance claims data and other administrative data sources in medicine. Results from several studies concerning the validity of administrative data varied significantly. Validity of these data sources depends on the clinical relevance of the diagnoses considered. The rate of implausible information was 0.04 %, while the validity of the considered diagnoses varied between 80 and 97 % across multiple validation studies. A matching study between health insurance claims data of the third-largest German health insurance provider, DAK-Gesundheit, and a prospective primary registry of the German Society for Vascular Surgery demonstrated a good level of validity regarding the mortality of endovascular and open surgical treatment of abdominal aortic aneurysm in German hospitals. In addition, a large-scale international comparison of administrative data for the same disorder presented important results in treatment reality, which differed from those from earlier randomized controlled trials. The importance of administrative data for research and quality improvement will continue to increase in the future. When discussing the internal and external validity of this data source, one has to distinguish not only between its intended usage (research vs. quality improvement), but also between the included diseases and/or treatment procedures. Linkage between primary registry data and administrative data could be a reasonable solution to some current major issues of validity.
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Short-term and long-term results of endovascular and open repair of abdominal aortic aneurysms in Germany

Background: Endovascular aortic repair (EVAR) has emerged as a standard of care for abdominal aortic aneurysm (AAA) repair. However, real‐world evidence to compare this technology to open aortic repair (OAR) is limited. Major gaps exist related to long‐term outcomes of therapies worldwide. Methods: Health insurance claims data of Germanys third largest insurance provider, DAK‐Gesundheit, were used to determine outcomes after interventions for intact AAA (iAAA) and ruptured AAA (rAAA). The study included patients operated on between October 2008 and April 2015. Results: Included were 5509 patients (3627 EVAR and 1859 OAR). Median follow‐up was 2.44 years (range, 0–6.46 years). The in‐hospital mortality was lower after EVAR compared with OAR for both iAAA (1.2% vs 5.4%) and rAAA (26.1% vs 42%; P < .001). Postoperative length of stay and occurrence of complications were also lower after EVAR. The in‐hospital mortality benefits of EVAR were most prominent in octogenarians (iAAA: EVAR, 2.2%; OAR, 18.2%; rAAA: EVAR, 34.4%; OAR, 62.3%; P < .001). However, the early survival benefit after EVAR reversed at ˜1.5 years, and Cox proportional hazard models revealed no differences in overall survival between EVAR and OAR. Landmark analysis focusing on patients surviving the procedure has shown lower survival in patients with EVAR. Conclusions: In this largest European investigation to date using health insurance claims data, we found that in‐hospital outcomes in Germany favor EVAR, which is comparable to findings reported in the United States and the United Kingdom. Trends toward lower long‐term survival after EVAR after discharge are important and require future research and reflection.

Outcome of Surgeon-Modified Fenestrated/Branched Stent-Grafts for Symptomatic Complex Aortic Pathologies or Contained Rupture

Purpose: To analyze the outcome of surgeon-modified fenestrated and branched stent-grafts (sm-FBSG) in high-risk patients with symptomatic complex aortic pathology or contained rupture. Methods: A single-center retrospective analysis was conducted of 21 consecutive patients (mean age 70 years, range 58–87; 16 men) treated with a sm-FBSG from April 2014 to September 2016. The indications included 11 thoracoabdominal and 10 pararenal aortic pathologies, which presented as symptomatic in 8 and as contained rupture in 13 patients. The mean aneurysm diameter was 7.4±2.3 cm. Results: Technical success was 100%. From 1 to 4 (mean 3) renovisceral branch vessels were targeted with fenestrations. The mean length of in-hospital stay was 19 days (range 1–78). There was 1 death within 30 days and 2 further in-hospital deaths. Two patients suffered permanent spinal cord injury, 2 developed respiratory failure, and 2 had renal failure requiring temporary or permanent dialysis. No myocardial infarction, stroke, or bowel ischemia occurred. Six early endoleaks (3 type II and 3 minor type III) were detected. Mean follow-up was 11.2 months (range 2–33) in 17 patients. One late aneurysm-related death occurred. All 13 follow-up imaging studies showed patent target renovisceral vessels, with 1 type I and 2 type II endoleaks. Conclusion: Sm-FBSG can be utilized for urgent treatment of complex abdominal and thoracoabdominal aortic pathologies in high-risk patients with anatomy unsuitable for commercially available stent-grafts.

Early Outcomes of the t-Branch Off-the-Shelf Multibranched Stent-Graft in Urgent Thoracoabdominal Aortic Aneurysm Repair

Purpose: To assess the short-term outcomes of the multibranched off-the-shelf t-Branch stent-graft for urgent thoracoabdominal aortic aneurysm (TAAA) repair and to evaluate the impact on outcomes of the learning curve and adherence to the instruction for use (IFU). Methods: Between 2014 and 2017, 42 patients (mean age 73.3±7 years; 26 men) underwent urgent TAAA treatment using the t-Branch stent-graft [18 in the early (2014–2015) period and 24 in the late (2016–2017) period]. Nearly half the patients were symptomatic (n=18) and 12 had contained rupture. Aneurysm diameter >80 mm was present in 12 (mean diameter 77.7±13.2 mm). Nineteen patients did not meet the IFU for the t-Branch due to target vessel anatomy. The primary endpoints were spinal cord ischemia (SCI), renal function impairment, and 30-day mortality. Target vessel patency and endoleak incidence were assessed at 30 days. Multivariate analyses examined associations between perioperative variables and outcomes; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Results: The technical success rate was 93% (39/42). Successful catheterization was achieved in 150/155 target vessels (97%). The postoperative SCI rate was 21% (5 paraplegia/4 transient paraparesis) and was correlated with age (OR 1.26, 95% CI 1.01 to 1.56, p=0.04). The renal function impairment rate was 23% (10/42; 2 temporary, 2 permanent dialysis) and was correlated with early experience (OR 7.74, 95% CI 1.3 to 43.9, p=0.019). The 30-day mortality was 14% (no intraoperative deaths); no factor was associated with mortality. During the first month, the incidences of type I, II, and III endoleaks were 0%, 43%, and 0%, respectively; branch patency was 99% (150/151). Procedure time decreased in the later experience (479±333 vs 407±25 minutes, p=0.09), though it was increased in cases outside the IFU (497±135 vs 389±118 minutes, p=0.009), along with fluoroscopy time (121±48 vs 92±33 minutes, p=0.036). Conclusion: Endovascular repair of urgent TAAA using the t-Branch is a feasible treatment option with acceptable 30-day mortality and morbidity in terms of SCI and renal function impairment. Adherence to the IFU prolonged procedure time but had no effect on outcomes. Increased experience of such cases over time may improve outcomes.

Gender differences in endovascular treatment of infrainguinal peripheral artery disease

BACKGROUND Despite ongoing research concerning comorbidities and clinical presentation of peripheral arterial disease (PAD), the issue of gender associated differences in treatment is far from being settled. PATIENTS AND METHODS This was a prospective, non-randomized multicentre study design. All patients suffering from intermittent claudication (IC) or critical limb ischaemia (CLI) were included. RESULTS A total of 2,798 procedures for symptomatic PAD in the infrainguinal region were recorded, with 1,696 (61.4 %) males. Distribution of comorbidities for patients with IC were gender-specifically different. Smoking was more common in men (41.9 vs. 31.9 %, p < .001), men had more often previous coronary heart disease (35.2 vs. 27.7 %, p = .007), and suffered more often from diabetes (33.9 vs. 28.2 %, p = .037). Women were generally older (71 vs. 77 years). Men were more prone to present with IC (46.9 vs. 43.6 %, p < .001) and ulcer/gangrene (43.6 vs. 41.2 %, p < .001). Women were more likely to present with rest pain (9.5 vs. 15.1 %, p < .001). Men were more often treated for a lesion below the knee (BTK) (21.1 vs. 14.9 %, p < .001), and females above the knee (ATK) (58.1 vs. 61.5 %, p < .001). Logistic regression analysis revealed a significant association of male gender and treatment for lesions BTK (OR 1.565, 95 % CI 1.281-1.913, p < .001). Dissections and bleeding complications were more often observed in females with IC (3.3 vs. 7.2 %, p = 0.003; 0.4 vs. 1.5 %, p = 0.044). Women were rather discharged to rehabilitation and had a longer hospital stay compared to men (3.4 vs. 8.9 %, p < .001; three vs. four days, p = .023). CONCLUSIONS The present study provides an overview on gender-specific differences in endovascular treatment of PAD. To date, available evidence on this topic is limited, emphasising the importance of further vascular research targeting this topic.

The Candy-Plug Technique: Technical Aspects and Early Results of a New Endovascular Method for False Lumen Occlusion in Chronic Aortic Dissection:

Purpose: To describe the technical aspects and early results of the Candy-Plug technique for endovascular false lumen occlusion in chronic aortic dissection. Methods: A retrospective single-center study analyzing 18 consecutive patients (mean age 63 years, range 44–76; 16 men) with thoracic false lumen aneurysm in chronic aortic dissection. All patients underwent thoracic endovascular aortic repair with false lumen occlusion using the Candy-Plug technique. Primary endpoints consisted of technical success (successful deployment) and clinical success (no false lumen backflow). Secondary endpoints included 30-day mortality and morbidity as well as aortic remodeling during follow-up. Results: Technical success was 100%. Additional intraprocedural false lumen embolization at the Candy-Plug level was needed in 1 patient due to persisting false lumen backflow on the final angiogram (clinical success 94%). There were no intraprocedural complications. In the perioperative period, there were 3 minor complications: transient mild spinal cord ischemia, cervical hematoma after carotid-subclavian bypass, and a common femoral artery pseudoaneurysm. No deaths or reinterventions occurred. Complete distal false lumen occlusion was present on postoperative computed tomography in 15 patients, while 3 had minor contrast enhancement in the distal false lumen. Over a mean 9-month follow-up (range 0–26), 1 patient died due to rupture. Follow-up >6 months was available in 10 patients (mean 14.7 months, range 7–26): 7 patients showed aortic remodeling, while aneurysm size was stable in 3 patients. Conclusion: The Candy-Plug technique is a feasible endovascular method to achieve false lumen occlusion and aortic remodeling in chronic aortic dissection. It is associated with low morbidity and mortality due to its minimal invasiveness.

Right brachial access is safe for branched endovascular aneurysm repair in complex aortic disease

Background: The risk of perioperative cerebrovascular events in endovascular repair of thoracic and thoracoabdominal aneurysms is reported from 2% to 15%. The unavoidable use of an upper extremity access during branched endovascular aneurysm repair (b‐EVAR) may play a role in embolic brain injuries. For this reason, some advocate the use of a left‐sided upper access to avoid crossing the origin of supra‐aortic vessels. However, the assumption that right brachial access has a higher risk for stroke during b‐EVAR has not been confirmed in the literature. Methods: This study retrospectively analyzed all consecutive patients treated by b‐EVAR with right brachial access at a single institution. A through‐and‐through right‐brachiofemoral 0.014‐inch wire was used to stabilize the sheath across the arch in all cases. End point of the study was the incidence of cerebrovascular events. Results: We identified 61 patients (65.6% male) during a 4‐year period. Mean age at the time of surgery was 70.4 years (range, 53‐87 years). The most common indication for treatment was type II (32.8%), followed by type IV thoracoabdominal aortic aneurysms (23%). There were 20 urgent (32.8%) and 41 elective (67.2%) procedures. Two perioperative ischemic strokes occurred in the first postoperative day in two men (3.3%; 95% confidence interval, 0.397‐11.84). No further ischemic strokes occurred perioperatively. There was no statistically significant association between the occurrence of postoperative stroke and any of the perioperative characteristics. No significant association was found between the duration of the procedure and the end point. In both patients with embolic events, the use of a left arm approach would not have been feasible due to coverage of the left subclavian artery ostium. Conclusions: The postoperative stroke rate in b‐EVAR with the use of a right brachial access in our experience was in line with the literature for treatment of thoracic and thoracoabdominal aortic aneurysms. We conclude that the right brachial access with the use of a stabilizing through‐and‐through wire is a safe approach during b‐EVAR.

Wie ist die Umsetzung eines AAA-Screening-Programms in Deutschland möglich?

ZusammenfassungHintergrundScreeningprogramme sind aktuell von hohem gesundheitspolitischen Interesse. Für das Ultraschallscreening auf abdominelle Aortenaneurysmen (AAA) bestehen international umfangreiche Studien, die auf die signifikante Reduktion der AAA-assoziierten Letalität verweisen. In Anbetracht dessen wurden in verschiedenen Ländern AAA-Screening-Programme mit unterschiedlicher Infrastruktur implementiert.ZielAuch in Deutschland soll ein AAA-Screening eingeführt werden. Die Umsetzung ist jedoch von unterschiedlichen Faktoren abhängig. In dieser Arbeit wird anhand einer Hausarztumfrage die Versorgungssituation in Deutschland beleuchtet und den Versorgungsstrukturen von Ländern gegenübergestellt, in denen das AAA-Screening bereits etabliert wurde. Anhand eines Vergleichs erfolgt eine Analyse, ob und unter welchen Vorgaben ein AAA-Screening in Deutschland umsetzbar ist.Material und MethodenMithilfe eines Fragebogens wurde eine bundesweite schriftliche Befragung von 2000 repräsentativ ausgewählten Hausärzten hinsichtlich ihrer Fachkenntnis zum Thema AAA, Ultraschallausstattung und Screening-Motivation durchgeführt.ErgebnisseEin Großteil der deutschen Hausärzte besitzt die nötige Fachkenntnis und Ultraschallfertigkeit zum Screening auf AAA. Mehr als zwei Drittel der befragten Ärzte verfügen über ein Ultraschallgerät. Die Mehrheit traut sich ein Screening zu. Etwa die Hälfte der Befragten ist motiviert, an einer Fortbildung zum Thema AAA teilzunehmen. Etwa drei Viertel der Befragten können sich die Implementierung eines Ultraschallscreenings auf AAA im Hausarztsektor vorstellen.SchlussfolgerungDie Grundvoraussetzungen einer bundesweiten Implementierung eines AAA-Screenings im Hausarztsektor sind auf der Basis von Fachkenntnis, Motivation und Ultraschallkapazität gegeben, und dessen Implementierung erscheint aufgrund einer einfacheren Umsetzbarkeit mit geringerem logistischen und finanziellen Aufwand im Vergleich zu ausländischen Modellen vorteilhaft.AbstractBackgroundScreening programs are currently of upmost importance in health politics. Large international studies of abdominal aortic aneurysm (AAA) screening programs showed a significant decrease in aneurysm-dependent mortality. In view of these findings, AAA screening programs have been implemented in various countries with variable healthcare infrastructures.AimIn Germany a screening program also urgently needs to be introduced but realization depends on a variety of factors. This article presents the health service system in Germany and compares it with countries that have already established AAA screening programs. A comparative analysis of factors influencing possible conditions for introducing an AAA screening program in Germany was carried out.Material and methodsA nationwide written survey of 2000 representatively chosen German family practitioners was carried out in order to evaluate their knowledge of AAAs, the availability of ultrasound devices and the motivation for performing the screening.ResultsA majority of German family practitioners possess the required knowledge of AAAs and the ultrasound skills to perform the screening. In addition, more than two thirds were in possession of an ultrasound device. Most practitioners were confident of performing a screening and would participate in a nationwide screening of AAAs.ConclusionThe conditions for a nationwide implementation of an AAA screening program performed with the help of general practitioners are fulfilled, considering knowledge, motivation und ultrasound availability. Owing to the lower logistic and financial expenditures in comparison to foreign AAA screening programs, the implementation by general practitioners seems to be advantageous.

How to Confirm Catheterization of Inner Branches in Aortic Endografting: The Universal Flush Test

Purpose: To describe a quick, simple, and reliable technique to confirm successful catheterization of a branched thoracic endograft’s inner branch. Technique: Accurate cannulation of inner branches can be verified through insertion and mild retraction of a Universal Flush angiographic catheter, whose tip hooks the branch and slightly opens. Conclusion: The use of an angiographic catheter with a curved tip is a safe and easy procedure that can be adopted to check the correct position inside the branch of an endograft designed for treatment of the aortic arch.