BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters.MethodsExosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed.ResultsPDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482).ConclusionWith exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.

Purpose: Prognostic inflammation-based parameters have been reported as useful tools in various oncologic diseases. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high mortality rate, making reliable prognostic markers highly desirable. However, there is still inconsistency in the literature regarding the efficacy of the different available scores. Methods: A total of 207 patients, who underwent primary resection of PDAC from January 2000 to December 2018 at the University Hospital of Erlangen, were included in this retrospective single-center study. Different biomarkers, including the preoperative neutrophil–lymphocyte ratio (NLR), the platelet–lymphocyte ratio (PLR), the c-reactive protein (CRP)–albumin ratio (CAR), the lymphocyte–CRP ratio (LCR), the prognostic nutritional index (PNI) and the modified Glasgow prognostic score (mGPS) were analyzed for their ability to predict overall survival (OS). Results: In our cohort, the median overall survival was 20.7 months. Among the investigated biomarkers, NLR and PNI were identified as independent prognostic markers (Hazard Ratio (HR) 1.6 (1.0–2.5), p = 0.048 and HR 0.6 (0.4–0.9), p = 0.018), whereas PLR, CAR, LCR and mGPS did not reach significance in the multivariate analysis. Subgroup analysis revealed that the prognostic value of NLR and PNI is particularly evident in locally advanced tumor stages (pT3/4 and pN+). Conclusions: The NLR and PNI could serve as valuable tools for estimating prognosis in patients with PDAC undergoing pancreatic resection in curative intention, especially in locally advanced tumor stages. However, conflicting results in the current literature highlight the need for further prospective studies to validate these findings.

(1) Background: The intake of aspirin (ASS) has been demonstrated to have a relevant impact on the pathogenesis, incidence and outcome in different solid gastrointestinal tumors. However, data on the effect of ASS on the short-term outcome and the long-term survival in patients with pancreatic carcinoma are still limited. (2) Methods: A total of 213 patients who underwent primary resection of PDAC at the University Hospital of Erlangen from January 2000 to December 2018 were included in this retrospective single-center study in total. Patients were stratified according to the aspirin intake into three groups: continuous aspirin intake (cASS), perioperatively interrupted aspirin intake (iASS) and no aspirin intake (no ASS) at the timepoint of surgery. The postoperative outcome as well as long-term survival were compared between the groups. (3) Results: There were no differences regarding postoperative morbidity (iASS: 54% vs. cASS: 53% vs. no ASS: 64%, p = 0.448) and in-hospital mortality (iASS: 4% vs. cASS: 10% vs. no ASS: 3%, p = 0.198) between the groups. The overall survival (OS) and disease-free survival (DFS) did not differ in the groups when comparing the ASS-intake status (OS: iASS 17.8 months vs. cASS 19.6 months vs. no ASS 21.6 months, p = 0.489; DFS: iASS 14.0 months vs. cASS 18.3 months vs. no ASS 14.7 months, p = 0.957). Multivariate analysis revealed that age (hazard ratio (HR) 2.2, p < 0.001), lymph node-positive status (HR 2.0, p < 0.001), R status 1 or 2 (HR 2.8, p < 0.001) and differentiation with a grading of 3 (HR 1.7, p = 0.005) were significant independent prognostic factors regarding the OS. Moreover, age (HR 1.5, p = 0.040), lymph node-positive status (HR 1.8, p = 0.002) and high-grade (G3) carcinomas (HR 1.5, p = 0.037) could be identified as independent prognostic parameters for DFS. (4) Conclusions: In patients undergoing primary surgery for curative resection of pancreatic carcinoma, the perioperative intake of ASS had no significant impact on postoperative outcome, overall and disease-free survival.

Purpose: To assess the technical (TS) and clinical success (CS) of CT fluoroscopy-guided drainage (CTD) in patients with symptomatic deep pelvic fluid collections following colorectal surgery. Methods: A retrospective analysis (years 2005 to 2020) comprised 43 drain placements in 40 patients undergoing low-dose (10–20 mA tube current) quick-check CTD using a percutaneous transgluteal (n = 39) or transperineal (n = 1) access. TS was defined as sufficient drainage of the fluid collection by ≥50% and the absence of complications according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). CS comprised the marked reduction of elevated laboratory inflammation parameters by ≥50% under minimally invasive combination therapy (i.v. broad-spectrum antibiotics, drainage) within 30 days after intervention and no surgical revision related to the intervention required. Results: TS was gained in 93.0%. CS was obtained in 83.3% for C-reactive Protein and in 78.6% for Leukocytes. In five patients (12.5%), a reoperation due to an unfavorable clinical outcome was necessary. Total dose length product (DLP) tended to be lower in the second half of the observation period (median: years 2013 to 2020: 544.0 mGy*cm vs. years 2005 to 2012: 735.5 mGy*cm) and was significantly lower for the CT fluoroscopy part (median: years 2013 to 2020: 47.0 mGy*cm vs. years 2005 to 2012: 85.0 mGy*cm). Conclusions: Given a minor proportion of patients requiring surgical revision due to anastomotic leakage, the CTD of deep pelvic fluid collections is safe and provides an excellent technical and clinical outcome. The reduction of radiation exposition over time can be achieved by both the ongoing development of CT technology and the increased level of interventional radiology (IR) expertise.

(1) Purpose: to evaluate the impact of age on postoperative short-term and long-term outcomes in patients undergoing curative pancreatic resection for PDAC. (2) Methods: This retrospective single-center study comprised 213 patients who had undergone primary resection of PDAC from January 2000 to December 2018 at the University Hospital of Erlangen, Germany. Patients were stratified according the age into two groups: younger (≤70 years) and older (>70 years) patients. Postoperative outcome and long-term survival were compared between the groups. (3) Results: There were no significant differences regarding inhospital morbidity (58% vs. 67%, p = 0.255) or inhospital mortality (2% vs. 7%, p = 0.073) between the two groups. The median overall survival (OS) and disease-free survival (DFS) were significantly shorter in elderly patients (OS: 29.2 vs. 17.1 months, p < 0.001, respectively; DFS: 14.9 vs. 10.4 months, p = 0.034). Multivariate analysis revealed that age was a significant independent prognostic predictor for OS and DFS (HR 2.23, 95% CI 1.58–3.15; p < 0.001 for OS and HR 1.62, 95% CI 1.17–2.24; p = 0.004 for DFS). (4) Conclusion: patient age significantly influenced overall and disease-free survival in patients with PDAC undergoing primary resection in curative intent.

(1) Purpose: To retrospectively assess the technical and clinical outcome of patients with symptomatic postoperative fluid collections after pancreatic surgery, treated with CT-guided drainage (CTD). (2) Methods: 133 eligible patients between 2004 and 2017 were included. We defined technical success as the sufficient drainage of the fluid collection(s) and the absence of peri-interventional complications (minor or major according to SIR criteria). Per definition, clinical success was characterized by normalization of specific blood parameters within 30 days after the intervention or a decrease by at least 50% without requiring additional surgical revision. C-reactive protein (CRP), Leukocytes, Interleukin-6, and Dose length product (DLP) for parts of the intervention were determined. (3) Results: 97.0% of 167 interventions were technically successful. Clinical success was achieved in 87.5% of CRP, in 78.4% of Leukocytes, and in 87.5% of Interleukin-6 assessments. The median of successful decrease was 6 days for CRP, 5 days for Leukocytes, and 2 days for Interleukin-6. No surgical revision was necessary in 93.2%. DLP was significantly lower in the second half of the observation period (total DLP: median 621.5 mGy*cm between 2011–2017 vs. median 944.5 mGy*cm between 2004–2010). (4) Conclusions: Technical success rate of CTD was very high and the clinical success rate was fair to good. Given an elderly and multimorbid patient cohort, CTD can have a temporizing effect in the postoperative period after pancreatic surgery. Reducing the radiation dose over time might reflect developments in CT technology and increased experience of interventional radiologists.

ZusammenfassungSchlaganfälle stehen als eine der führenden Todesursache weltweit auf Platz zwei nach KHK/Herzinfarkt und gehören zu den häufigsten Ursachen für Invalidität im höheren Lebensalter. In der vorliegenden Kasuistik wird der Fall einer Patientin mit spinalem Schlaganfall aufgearbeitet. Bei plötzlich einsetzender Paraplegie mit dissoziierter Empfindungsstörung wurde ein arterioarteriell embolischer Arteria-spinalis-anterior-Infarkt diagnostiziert. Durch ein prä- sowie innerklinisch zielgerichtetes Vorgehen war es möglich, der Patientin in einem individuellen Heilversuch eine Lysetherapie anzubieten. Nach erfreulichem klinischem Verlauf war die Patientin 17 Tage nach dem Ereignis bereits auf kurzen Distanzen wieder gehfähig.

Zusammenfassung Schlaganfalle stehen als eine der fuhrenden Todesursache weltweit auf Platz zwei nach KHK/Herzinfarkt und gehoren zu den haufigsten Ursachen fur Invaliditat im hoheren Lebensalter. In der vorliegenden Kasuistik wird der Fall einer Patientin mit spinalem Schlaganfall aufgearbeitet. Bei plotzlich einsetzender Paraplegie mit dissoziierter Empfindungsstorung wurde ein arterioarteriell embolischer Arteria-spinalis-anterior-Infarkt diagnostiziert. Durch ein pra- sowie innerklinisch zielgerichtetes Vorgehen war es moglich, der Patientin in einem individuellen Heilversuch eine Lysetherapie anzubieten. Nach erfreulichem klinischem Verlauf war die Patientin 17 Tage nach dem Ereignis bereits auf kurzen Distanzen wieder gehfahig.Abstract Strokes are the second leading cause of death worldwide after CHD/heart attack and are one of the most common cause of disability in old age. In the present case report a patient with spinal stroke is reviewed. In the case of sudden onset paraplegia with dissociated sensory disturbance, the patient was diagnosed with arterio-arterial embolic anterior spinal artery infarction. By means of a preclinical as well as internal clinical targeted approach, it was possible to offer the patient an individual healing attempt with lysis therapy. After an encouraging clinical course, the patient was able to walk again within short distances 17 days after the event.

OBJECTIVES Existing surgical sealants fail to combine design requirements, such as sealing performance, on-demand activation and biocompatibility. The aim of this study was to compare the effectiveness and safety of the SETALIUM™ Vascular Sealant (SVS), a novel, on-demand activatable sealant, with the commercial sealant, BioGlue®, for the repair of vascular defects. METHODS In an in vivo porcine model, the use of SVS was compared with BioGlue, for sealing 2-mm defects of the carotid artery and jugular vein. Animals were followed for 7 days and 5 weeks (each time point and per experimental group, n = 4), respectively. The degree of stenosis and flow velocity was determined, and the local tissue response was evaluated. RESULTS In vivo incision closure succeeded in all cases, and SVS was superior in clinical usability, enabled by its on-demand activation. Unlike BioGlue, SVS use did not induce stenosis and was associated with physiological blood flow in all cases. Moreover, closure with SVS was associated with a low inflammatory reaction and no thrombus formation or intima proliferation, in contrast to BioGlue. CONCLUSIONS SVS demonstrated effective and rapid sealing of 2-mm vascular defects, with favourable biocompatibility compared to BioGlue. Thus, SVS seems to be an effective and safe vascular sealant.

Objectives: Transcatheter closure of atrial septal defects (ASD) and patent foramen ovale (PFO) is the therapeutic gold-standard. However, current devices consist of a lot of foreign material and are stiff, and therefore cannot adapt to the anatomy. The underlying mechanism of fixation relies on compression which can lead to tissue damage and complete heart blocks, for example. Thus, there is a big need for alternative materials and closure techniques. The aim of the study was evaluation of closure approaches with flexible patch materials and tissue adhesives in an in vitro burst pressure setup and an ex vivo beating heart model.