Christiane J. Bruns

Gasless Videoendoscopic Implantation of an Aortobifemoral Vascular Prosthesis via a Transperitoneal versus Extraperitoneal Approach: An Experimental Study

Purpose: To report progress in the development of a new minimally invasive surgical technique for aortobifemoral grafting utilizing gasless videoendoscopy. Methods: In an experimental study, aortobifemoral Dacron vascular prostheses were implanted in 20 human cadavers using videoendoscopic techniques in both transperitoneal and extraperitoneal approaches. Rather than inducing pneumoperitoneum, the abdominal wall was elevated with an electrically powered lifting system. Results: Each approach was utilized in 10 cadavers for implantation of 20 aortobifemoral grafts under endoscopic guidance in a gasless field. Average operative time for the transperitoneal approach was 3.8 hours (range 3.0 to 5.5), slightly less than the average 4.1 hours (range 3.0 to 6.0) for the extraperitoneal access. Both access routes provided adequate visualization of the operative field. Conclusions: Advantages of gasless endoscopy include the use of conventional instruments and the potential benefits associated with a minimally invasive approach. Optical magnification facilitates suturing of the femoral anastomosis, improves examination of the vascular walls, and allows a more accurate suturing technique.

Results of endoscopic vacuum-assisted closure device for treatment of upper GI leaks

BackgroundEsophageal perforations and postoperative leakage of esophagogastrostomies are considered to be life-threatening conditions due to the potential development of mediastinitis and consecutive sepsis. Vacuum-assisted closure (VAC) techniques, a well-established treatment method for superficial infected wounds, are based on a negative pressure applied to the wound via a vacuum-sealed sponge. Endoluminal VAC (E-VAC) therapy as a treatment for GI leakages in the rectum was introduced in 2008. E-VAC therapy is a novel method, and experience regarding esophageal applications is limited. In this retrospective study, the experience of a high-volume center for upper GI surgery with E-VAC therapy in patients with leaks of the upper GI tract is summarized. To our knowledge, this series presents the largest patient cohort worldwide in a single-center study.MethodsBetween October 2010 and January 2017, 77 patients with defects in the upper gastrointestinal tract were treated using the E-VAC application. Six patients had a spontaneous perforation, 12 patients an iatrogenic injury, and 59 patients a postoperative leakage in the upper gastrointestinal tract.ResultsComplete restoration of the esophageal defect was achieved in 60 of 77 patients. The average duration of application was 11.0 days, and a median of 2.75 E-VAC systems were used. For 21 of the 77 patients, E-VAC therapy was combined with the placement of self-expanding metal stents.ConclusionThis study demonstrates that E-VAC therapy provides an additional treatment option for esophageal wall defects. Esophageal defects and mediastinal abscesses can be treated with E-VAC therapy where endoscopic stenting may not be possible. A prospective multi-center study has to be directed to bring evidence to the superiority of E-VAC therapy for patients suffering from upper GI defects.

In vivo biomechanical properties of three different graft materials in peripheral vascular surgery

Compliance is one of the most decisive biomechanical characteristic features of the graft wall as well as the vessel wall influencing the success of vascular reconstruction.In the following study we noninvasively investigated graft-arterial compliance alterationsin vivo after surgery with M-mode ultrasound in 99 patients with various graft materials over an extended follow-up period between 3 months and 10 years.During a one year periodin vivo graft compliance was measured with M-mode ultrasound in 49 implanted bifurcation grafts and 68 femoropopliteal reconstructions of 99 patients (25 female and 74 male). For bifurcation grafts Dacron and for femoropopliteal reconstruction either Dacron, polytetrafluoroethylene (PTFE) or autologous saphenous vein were used.Thein vivo compliance of gel-coated Dacron bifurcation grafts and femoropopliteal grafts declined with increasing time following implantation.The compliance of bifurcation grafts depended on the patency of the outflow tract. In case of an occluded superficial femoral artery with main outflow through the deep femoral artery graft compliance declined about 51% over 5 years after implantation. In contrast, in case of a patent superficial artery the reduction of graft compliance was only 37%.In all femoropopliteal grafts the decrease of graft compliance over 5 years after implantation depended on the graft material. With a better initial compliance autologous vein grafts were more compliant at all times in the follow-up in comparison with PTFE or Dacron grafts.The ability to measure noninvasively in vivo graft compliance with M-mode ultrasound may enable to estimate early patency problems and at least graft failure depending on graft material and time after implantation.

Distinct Pathogenesis of Pancreatic Cancer Microvesicle–Associated Venous Thrombosis Identifies New Antithrombotic Targets In Vivo

Objective— Cancer patients are at high risk of developing deep venous thrombosis (DVT) and venous thromboembolism, a leading cause of mortality in this population. However, it is largely unclear how malignant tumors drive the prothrombotic cascade culminating in DVT. Approach and Results— Here, we addressed the pathophysiology of malignant DVT compared with nonmalignant DVT and focused on the role of tumor microvesicles as potential targets to prevent cancer-associated DVT. We show that microvesicles released by pancreatic adenocarcinoma cells (pancreatic tumor–derived microvesicles [pcMV]) boost thrombus formation in a model of flow restriction of the mouse vena cava. This depends on the synergistic activation of coagulation by pcMV and host tissue factor. Unlike nonmalignant DVT, which is initiated and propagated by innate immune cells, thrombosis triggered by pcMV was largely independent of myeloid leukocytes or platelets. Instead, we identified externalization of the phospholipid phosphatidylethanolamine as a major mechanism controlling the prothrombotic activity of pcMV. Disrupting phosphatidylethanolamine-dependent activation of factor X suppressed pcMV-induced DVT without causing changes in hemostasis. Conclusions— Together, we show here that the pathophysiology of pcMV-associated experimental DVT differs markedly from innate immune cell–promoted nonmalignant DVT and is therefore amenable to distinct antithrombotic strategies. Targeting phosphatidylethanolamine on tumor microvesicles could be a new strategy for prevention of cancer-associated DVT without causing bleeding complications.

Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection.DesignPatients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread.DiscussionPancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy.Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer.Trial registrationGerman Clinical Trials Register, DRKS00006179.

Stellenwert der Desobliteration der Beckenetage

Die Implantation von prothetischem Material hat die Behandlungsmoglichkeiten der arteriellen Verschluskrankheit in der Beckenetage erheblich erweitert. Komplikationen, die hierbei jedoch auftreten konnen, insbesondere sei die infizierte intraabdominelle Prothese erwahnt, geben vielfach Anlas zum Zuruckbesinnen auf alternative Operationsverfahren. Im eigenen Patientengut wurden daher die in den letzten 5 Jahren durchgefuhrten iliakalen Desobliterationen nachuntersucht.

CD36-triggered cell invasion and persistent tissue colonization by tumor microvesicles during metastasis

Tumor microvesicles are a peculiar type of extracellular vesicles that circulate in the blood of patients with metastatic cancer. The itineraries and immune cell interactions of tumor microvesicles during the intravascular and extravascular stages of metastasis are largely unknown. We found that the lipid receptor CD36 is a major mediator of the engulfment of pancreatic tumor microvesicles by myeloid immune cells in vitro and critically samples circulating tumor microvesicles by resident liver macrophages in mice in vivo. Direct nanoscopic imaging of individual tumor microvesicles shows that the microvesicles rapidly decay during engulfment whereby their cargo is targeted concomitantly to the plasma membrane and the cytoplasm excluding lysosomal compartments. CD36 also promotes internalization of blood cell (nontumor) microvesicles, which involves endolysosomal pathways. A portion of tumor microvesicles circulating in the liver microcirculation traverses the vessel wall in a CD36‐dependent way. Extravasated microvesicles colonize distinct perivascular Ly6C− macrophages for at least 2 wk. Thus, the microvesicles are increasingly integrated into CD36‐induced premetastatic cell clusters and enhance development of liver metastasis. Hence, promotion of metastasis by pancreatic tumor microvesicles is associated with CD36‐regulated immune cell invasion and extravasation of microvesicles and persistent infiltration of specific tissue macrophages by microvesicle cargo.—Pfeiler, S., Thakur, M., Grünauer, P., Megens, R. T. A., Joshi, U., Coletti, R., Samara, V., Müller‐Stoy, G., Ishikawa‐Ankerhold, H., Stark, K., Klingl, A., Fröhlich, T., Arnold, G. J., Wörmann, S., Bruns, C. J., Algül, H., Weber, C., Massberg, S., Engelmann, B. CD36‐triggered cell invasion and persistent tissue colonization by tumor microvesicles during metastasis. FASEB J. 33, 1860–1872 (2019). www.fasebj.org

Ösophaguskarzinom inkl. Karzinome des gastroösophagealen Übergangs

In der Behandlung von Patienten mit lokalisierten Osophaguskarzinomen (Tis, T1a und T1b ohne Risikofaktoren, <2 cm) haben sich endoskopischen Verfahren als ausreichende Alternative zur chirurgischen Therapie durchgesetzt. Fur Patienten mit resektabler Erkrankung ab T1b stellt die Osophagektomie mit Interposition eines Schlauchmagens oder in selteneren Fallen eines Kolon- oder Dunndarminterponates das chirurgische Vorgehen der Wahl dar. Fur Patienten mit resektablen Tumoren des gastroosophagealen Ubergangs werden sowohl die Osophagektomie als auch die transhiatal erweiterte Gastrektomie durchgefuhrt. Eine neoadjuvante Vorbehandlung hat sich fur fortgeschrittene Stadien ab cT2 durchgesetzt. Eine definitive Radiochemotherapie scheint fur Plattenepithelkarzinome vergleichbare onkologische Ergebnisse zu erzielen und wird in den Leitlinien als Alternative berucksichtigt. Bei einem Rezidiv nach definitiver Radiochemotherapie ist eine Salvage-Osophagektomie moglich.

4D flow MRI for the analysis of celiac trunk and mesenteric artery stenoses

PURPOSE This study aims to assess the feasibility of 4D flow MRI measurements in complex vascular territories; namely, the celiac artery (CA) and superior mesenteric artery (SMA). MATERIALS AND METHODS In this prospective study, 22 healthy volunteers and 10 patients were scanned at 3 T. Blood flow parameters were compared between healthy volunteers and patients with stenosis of the CA and/or SMA as a function of stenosis grade characterized by prior contrast-enhanced computed tomography (CE-CT). The 4D flow MRI acquisition covered the CA, SMA and adjusting parts of the abdominal aorta (AO). Measurements of velocity- (peak velocity [PV], average velocity [AV]) and volume-related parameters (peak flow [PF], stroke volume [SV]) were conducted. Further, stenosis grade and wall shear stress in the CA, SMA and AO were evaluated. RESULTS In patients, prior evaluation by CE-CT revealed 11 low- and 5 mid-grade stenoses of the CA and/or SMA. PV and AV were significantly higher in patients than in healthy volunteers [PV: p < 0.0001; AV: p = 0.03, p < 0.001]. PF and SV did not differ significantly between healthy volunteers and patients; however, a trend towards lower PF and SV could be detected in patients with mid-grade stenoses. Comparison of 4D flow MRI with CE-CT revealed a strong positive correlation in estimated degree of stenosis (CA: r = 0.86, SMA: r = 0.98). Patients with mid-grade stenoses had a significantly higher average WSS magnitude (AWM) than healthy volunteers (p = 0.02). CONCLUSION This feasibility study suggests that 4D flow MRI is a viable technique for the evaluation of complex flow characteristics in small vessels such as the CA and SMA. 4D flow MRI approves comparable to the morphologic assessment of complex vascular territories using CE-CT but, in addition, offers the functional evaluation of flow parameters that goes beyond the morphology.

Lungenkrebs bei operierten Nichtrauchern

Hintergrund.Die wichtigste Ursache für die Entstehung von Lungenkrebs ist das inhalative Rauchen. Bei Männern gehen nach Angabe des Robert Koch-Instituts 9 von 10, bei Frauen mindestens 6 von 10 Lungenkrebserkrankungen auf aktivesRauchen zurück. In einer vielversprechendenklinischenStudie verglichenStiles et al. das krankheitsfreie Intervall sowie das lungenkrebsspezifische Überleben nach Lungenresektionen bei Nierauchern und aktiven Rauchern.