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Background The question of the ideal neoadjuvant therapy for locally advanced esophagogastric adenocarcinoma has not been answered to date. Multimodal treatment has become a standard treatment for these adenocarcinomas. Currently, perioperative chemotherapy (FLOT) or neoadjuvant chemoradiation (CROSS) is recommended. Methods A monocentric retrospective analysis compared long-term survival after CROSS versus FLOT. The study enrolled patients with adenocarcinoma of the esophagus (EAC) or the esophagogastric junction type I or II undergoing oncologic Ivor–Lewis esophagectomy between January 2012 and December 2019. The primary objective was to determine the long-term outcome in terms of overall survival. The secondary objectives were to determine differences regarding the histopathologic categories after neoadjuvant treatment and the histomorphologic regression. Results The findings showed no survival advantage for one or the other treatment in this highly standardized cohort. All the patients underwent open (CROSS: 9.4% vs. FLOT: 22%), hybrid (CROSS: 82% vs. FLOT: 72%), or minimally invasive (CROSS: 8.9% vs. FLOT: 5.6%) thoracoabdominal esophagectomy. The median post-surgical follow-up period was 57.6 months (95% confidence interval [CI] 23.2–109.7 months), and the median survival was longer for the CROSS patients (54 months) than for the FLOT patients (37.2 months) (p = 0.053). The overall 5-years survival was 47% for the entire cohort (48% for the CROSS and 43% for the FLOT patients). The CROSS patients showed a better pathologic response and fewer advanced tumor stages. Conclusion The improved pathologic response after CROSS cannot be translated into longer overall survival. To date, the choice of which neoadjuvant treatment to use can be made only on the basis of clinical parameters and the patient’s performance status.

Purpose Surgical oncologists are frequently confronted with the question of expected long-term prognosis. The aim of this study was to apply machine learning algorithms to optimize survival prediction after oncological resection of gastroesophageal cancers. Methods Eligible patients underwent oncological resection of gastric or distal esophageal cancer between 2001 and 2020 at Heidelberg University Hospital, Department of General Surgery. Machine learning methods such as multi-task logistic regression and survival forests were compared with usual algorithms to establish an individual estimation. Results The study included 117 variables with a total of 1360 patients. The overall missingness was 1.3%. Out of eight machine learning algorithms, the random survival forest (RSF) performed best with a concordance index of 0.736 and an integrated Brier score of 0.166. The RSF demonstrated a mean area under the curve (AUC) of 0.814 over a time period of 10 years after diagnosis. The most important long-term outcome predictor was lymph node ratio with a mean AUC of 0.730. A numeric risk score was calculated by the RSF for each patient and three risk groups were defined accordingly. Median survival time was 18.8 months in the high-risk group, 44.6 months in the medium-risk group and above 10 years in the low-risk group. Conclusion The results of this study suggest that RSF is most appropriate to accurately answer the question of long-term prognosis. Furthermore, we could establish a compact risk score model with 20 input parameters and thus provide a clinical tool to improve prediction of oncological outcome after upper gastrointestinal surgery.

Radiological reports of pancreatic lesions are currently widely formulated as free texts. However, for optimal characterization, staging and operation planning, a wide range of information is required but is sometimes not captured comprehensively. Structured reporting offers the potential for improvement in terms of completeness, reproducibility and clarity of interdisciplinary communication. Interdisciplinary consensus finding of structured report templates for solid and cystic pancreatic tumors in computed tomography (CT) and magnetic resonance imaging (MRI) with representatives of the German Society of Radiology (DRG), German Society for General and Visceral Surgery (DGAV), working group Oncological Imaging (ABO) of the German Cancer Society (DKG) and other radiologists, oncologists and surgeons. Among experts in the field of pancreatic imaging, oncology and pancreatic surgery, as well as in a public online survey, structured report templates were developed by consensus. These templates are available on the DRG homepage under www.befundung.drg.de and will be regularly revised to the current state of scientific knowledge by the participating specialist societies and responsible working groups. This article presents structured report templates for solid and cystic pancreatic tumors to improve clinical staging (cTNM, ycTNM) in everyday radiology. · Structured report templates offer the potential of optimized radiological reporting with regard to completeness, reproducibility and differential diagnosis.. · This article presents consensus-based, structured reports for solid and cystic pancreatic lesions in CT and MRI.. · These structured reports are available open source on the homepage of the German Society of Radiology (DRG) under www.befundung.drg.de..· Persigehl T, Baumhauer M, Baeßler B et al. Structured Reporting of Solid and Cystic Pancreatic Lesions in CT and MRI: Consensus-Based Structured Report Templates of the German Society of Radiology (DRG). Fortschr Röntgenstr 2020; 192: 641 - 655. In der klinischen Radiologie werden aktuell radiologische Befundberichte bei Pankreasläsionen weitverbreitet als Freitexte formuliert. Für die optimale klinische Versorgung, das Staging und die Operationsplanung sind mannigfaltige Informationen erforderlich, die mitunter nicht umfänglich erfasst werden. Die strukturierte Befundung bietet hier das Potenzial einer Verbesserung in Bezug auf Vollständigkeit, Reproduzierbarkeit sowie Klarheit der interdisziplinären Kommunikation. Interdisziplinäre Erstellung von strukturierten Befundvorlagen für solide und zystische Pankreastumoren in der Computertomografie (CT) und in der Magnetresonanztomografie (MRT) mit Vertretern der Deutschen Röntgengesellschaft (DRG), der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV), der Arbeitsgemeinschaft Onkologische Bildgebung (ABO) der Deutschen Krebsgesellschaft (DKG) sowie weiteren Radiologen, Onkologen und Chirurgen. Unter Experten auf dem Gebiet der Pankreasbildgebung, onkologischen Versorgung und Pankreaschirurgie sowie in einer öffentlichen Online-Umfrage wurden strukturierte Befundvorlagen im Konsensus-Verfahren entwickelt, die im weiteren Verlauf regelmäßig durch die beteiligten Fachgesellschaften und verantwortlichen Arbeitsgemeinschaften auf den aktuellen Stand der wissenschaftlichen Erkenntnis angepasst werden sollen. Dieser Artikel stellt strukturierte Befundvorlagen für solide und zystische Pankreastumoren vor, die im radiologischen Alltag helfen sollen, das klinische Staging (cTNM, ycTNM) zu verbessern. · Strukturierte Befundvorlagen bieten das Potenzial einer optimierten radiologischen Befundung in Bezug auf Vollständigkeit, Reproduzierbarkeit und Differenzialdiagnose.. · Dieser Artikel stellt Konsensus-basierte, strukturierte Befundvorlagen für solide und zystische Pankreasläsionen im CT und MRT vor.. · Die von der Deutsche Röntgengesellschaft entwickelten Befundvorlagen werden unter www.befundung.drg.de zur Verfügung gestellt..· Persigehl T, Baumhauer M, Baeßler B et al. Structured Reporting of Solid and Cystic Pancreatic Lesions in CT and MRI: Consensus-Based Structured Report Templates of the German Society of Radiology (DRG). Fortschr Röntgenstr 2020; 192: 641 – 656.

Background According to current guidelines, treatment of patients with hepatic oligometastasis in pancreatic cancer is not reflected and systemic chemotherapy is recommended in those patients. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from clinical trials addressing this particular patient group is not available. Methods In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. The clinical trial will focus on a well-defined patient collective with metastatic load limited to the liver as target organ with a maximum of five metastases. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (nal-IRI + OX+ 5-FU/FA, NAPOX) was chosen as neoadjuvant chemotherapy; the choice was based on an ongoing clinical study in which NAPOX appeared manageable, with promising anti-tumor activity in first-line treatment of patients with metastatic pancreatic adenocarcinoma. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. Discussion This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Trial registration numbers EudraCT 2019–002734-37; NCT04617457.

Background Recent findings support the hypothesis of sex-related differences in inflammatory and immunological responses to trauma. The aim of this study was to address sex-specific aspects in patients who underwent pancreatic surgery. Methods This retrospective study used data from the German StuDoQ registry. Patients who underwent pancreatic surgery between 2010 and 2020 were stratified according to procedure (pancreatic head resection, distal pancreatectomy (DP), total pancreatectomy (TP)). Each cohort underwent propensity score matching (PSM) with the co-variables BMI, ASA, age, coronary heart disease (CHD), diabetes, hypertension with medication, and histology to level the distribution of co-morbidities between men and women. The main outcomes were morbidity and mortality. Results The total cohort consisted of 10 224 patients (45.3 per cent women). Men had higher ASA grades, and more often had CHD, diabetes, and hypertension with medication. Women had fewer overall complications (57.3 versus 60.1 per cent; P = 0.005) and a lower mortality rate (3.4 versus 4.9 per cent; P Conclusion Women had favourable outcomes after pancreatic surgery.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. PDAC prognostic and diagnostic biomarkers are still being explored. The aim of this study is to establish a robust molecular signature that can improve the ability to predict PDAC prognosis. 155 overlapping differentially expressed genes between tumor and non-tumor tissues from three Gene Expression Omnibus (GEO) datasets were explored. A least absolute shrinkage and selection operator method (LASSO) Cox regression model was employed for selecting prognostic genes. We developed a 6-mRNA signature that can distinguish high PDAC risk patients from low risk patients with significant differences in overall survival (OS). We further validated this signature prognostic value in three independent cohorts (GEO batch, P < 0.0001; ICGC, P = 0.0036; Fudan, P = 0.029). Furthermore, we found that our signature remained significant in patients with different histologic grade, TNM stage, locations of tumor entity, age and gender. Multivariate cox regression analysis showed that 6-mRNA signature can be an independent prognostic marker in each of the cohorts. Receiver operating characteristic curve (ROC) analysis also showed that our signature possessed a better predictive role of PDAC prognosis. Moreover, the gene set enrichment analysis (GSEA) analysis showed that several tumorigenesis and metastasis related pathways were indeed associated with higher scores of risk. In conclusion, identifying the 6-mRNA signature could provide a valuable classification method to evaluate clinical prognosis and facilitate personalized treatment for PDAC patients. New therapeutic targets may be developed upon the functional analysis of the classifier genes and their related pathways.

Pancreatic cancer is a complex disease and knowledge about precursor lesions, its molecular biological properties and tumorigenesis has considerably grown. Especially during the last decade, new insights into the molecular biology of PDAC helped to generate a better understanding of the disease development. Four driver genes were identified (KRAS oncogene, CDKN2A, p53, and SMAD4 tumor suppressor genes) but besides those, a large number of infrequently mutated genes dominate the mutation spectrum within PDAC. Apart from sequential tumorigenesis, chromothripsis has emerged as an underlying key mechanism for PDAC development. One key characteristic of PDAC is its dense stroma that is partly responsible for chemotherapy resistance. Pancreatic cancer has a huge potential for metastasis and one underlying mechanism, though controversially discussed, is epithelial to mesenchymal transition (EMT).

Magnetospirillum gryphiswaldense employs iron-rich nanoparticles for magnetic navigation within environmental redox gradients. This behavior termed magneto-aerotaxis was previously shown to rely on the sensory pathway CheOp1, but the precise localization of CheOp1-related chemoreceptor arrays during the cell cycle and its possible interconnection with three other chemotaxis pathways have remained unstudied. Here, we analyzed the localization of chemoreceptor-associated adaptor protein CheW(1) and histidine kinase CheA(1) by superresolution microscopy in a spatiotemporal manner. CheW(1) localized in dynamic clusters that undergo occasional segregation and fusion events at lateral sites of both cell poles. Newly formed smaller clusters originating at midcell before completion of cytokinesis were found to grow in size during the cell cycle. Bipolar CheA(1) localization and formation of aerotactic swim halos were affected depending on the fluorescent protein tag, indicating that CheA(1) localization is important for aerotaxis. Furthermore, polar CheW(1) localization was independent of cheOp2 to cheOp4 but lost in the absence of cheOp1 or cheA(1). Results were corroborated by the detection of a direct protein interaction between CheA(1) and CheW(1) and by the observation that cheOp2- and cheOp3-encoded CheW paralogs localized in spatially distinct smaller clusters at the cell boundary. Although the findings of a minor aerotaxis-related CheOp4 phenotype and weak protein interactions between CheOp1 and CheOp4 by two-hybrid analysis implied that CheW(1) and CheW(4) might be part of the same chemoreceptor array, CheW(4) was localized in spatially distinct polar-lateral arrays independent of CheOp1, suggesting that CheOp1 and CheOp4 are also not connected at the molecular level. IMPORTANCE Magnetotactic bacteria (MTB) use the geomagnetic field for navigation in aquatic redox gradients. However, the highly complex signal transduction networks in these environmental microbes are poorly understood. Here, we analyzed the localization of selected chemotaxis proteins to spatially and temporally resolve chemotaxis array localization in Magnetospirillum gryphiswaldense. Our findings suggest that bipolar localization of chemotaxis arrays related to the key signaling pathway CheOp1 is important for aerotaxis and that CheOp1 signaling units assemble independent of the three other chemotaxis pathways present in M. gryphiswaldense. Overall, our results provide deeper insights into the complex organization of signaling pathways in MTB and add to the general understanding of environmental bacteria possessing multiple chemotaxis pathways.

Background Secondary lymphoid organs (SLO) are involved in induction and enhancement of anti-tumor immune responses on different tumor entities. Recent evidence suggests that anti-tumor immune responses may also be induced or enhanced in the tumor microenvironment in so called tertiary lymphoid structures (TLS). It is assumed that TLS represent a hotspot for T cell priming, B cell activation, and differentiation, leading to cellular and humoral anti-tumor immune response. Methods FFPE-slides of 120 primary pancreatic ductal adenocarcinoma (PDAC) patients were immunohistochemically (IHC) stained for CD20, CD3, CD8 and HLA-ABC to analyze spatial distribution of tumor-infiltrating lymphocytes. 5-color immunofluorescence staining was performed to further investigate structural components of TLS in comparison to lymphoid follicles in SLOs. Microscope-based laser microdissection and Nanostring-base RNA expression analysis were used to compare gene expression in PDAC, TLS, SLOs and normal pancreatic tissue. Results TLS were frequently detected in PDAC and were mainly localized along the invasive tumor margin. In less than 10% of the cases TLS were infiltrating the tumors. Interestingly, 20% of the patients had no TLS. Results of TLS will be correlated with clinical parameters, Immunoscore and immune escape mechanisms. 5-color Immunofluorescence staining revealed similar organization and function of TLS and SLO. Finally, gene expression analyzed by Nanostring revealed largely overlapping expression patterns in TLS and SLO. Conclusions The results clearly demonstrate close similarities between SLO and TLS in terms of composition, distribution and gene expression Patterns. Disclosure Information M. Thelen: None. M.A. Garcia-Marquez: None. T. Nestler: None. S. Wagener-Ryczek: None. J. Lehmann: None. E. Staib: None. F. Popp: None. F. Gebauer: None. P. Lohneis: None. M. Odenthal: None. S. Merkelbach-Bruse: None. C. Bruns: None. K. Wennhold: None. M. von Bergwelt-Baildon: None. H.A. Schloser: None.

Power-to-gas (P2G) is referred to technologies that convert carbon dioxide into methane. Both bio- and chemical catalysts may be used for conversion purposes. One of the most disruptive biotechnologies was developed by the University of Chicago (IL) (publication number: EP2661511B1), using a robust, highly selective, patented strain of Archaea. Electrochaea GmbH has developed an innovative bench-scale P2G prototype unit, which uses this highly efficient Archaea strain, specialized components and specifically developed control strategies. The structure and the components of the prototype are equivalent with the functional parts of the currently largest commercial scale biomethanation BioCat plant located in Avedøre, Denmark (www.biocat-project.com). Power-to-Gas Hungary Kft. has committed to further develop this innovative technology. The first steps of this development have been taken by operating the benchscale unit and analyzing the data of the operating periods. The prototype is operated based on weekly campaigns. During continuous operation, H2O is generated as a by-product of methane. Therefore, approximately 200 ml of biocatalyst is discharged each day and concentrated media containing macro and micronutrients are injected into the reactor to maintain media composition. The laboratory staff records all gas composition data each morning. The gas composition is measured every 12 minutes by an Awite AwiFlex Cool+ gas analyzer. Within this article, we analyze the collected datasets containing more than 12 000 records and present the first practical experiences of the operations of the innovative power-to-gas bench-scale prototype. The analysis of the collected gas composition data of the product gas already provides important data for modelling the commercial-scaled processes. The average value of VVD was about 40 l/l/d in the period under review. Further increase of the methane content can be achieved by introduction of higher mixing energy and by increasing pressure levels in the bioreactor (as demonstrated in the BioCat plant – data not shown here) – both of which are strategies envisioned for the commercial plant. In routine activities (turn on, shut down, continuous operation) we could verify the high robustness of the biocatalyst and the base connection between the registered datasets and performed test results.

Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3.6pl) and one established gemcitabine resistant cell variant-L3.6plGres. Second, we analyzed the protein expression in tissue microarrays (TMA) from specimens of 254 radically resected patients with pancreatic adenocarcinoma. The prognostic relevance of IFIT3 was evaluated by the Kaplan–Meier and Cox regression analysis. L3.6pl cells with an aggressive capacity showed a significant higher expression of IFIT3 as compared to FG cells. IFIT3 was accumulated in gemcitabine resistant cells. Overexpression of IFIT3 increased the resistance of apoptosis against gemcitabine treatment. Patients who had high expression of IFIT3 (32%) and received chemotherapy had a statistically significant reduced survival in multivariate analysis. High expression of IFIT3 enhances anti-apoptotic activity and chemotherapy resistance of PDAC cells. High expression of IFIT3 was independently correlated to shorter patients’ survival and may serve as a prognostic marker.

Background: In the present study we review and discuss the current evidence and suggest how to proceed in the management of oligometastatic disease in upper gastrointestinal cancer. Methods: An electronic search of the PubMed database for relevant articles was performed. Results: Both the search for ‘oligometastasis', ‘oligometastases', ‘oligometastatic', ‘oligometastatic disease' as well as ‘esophageal' and ‘esophageal cancer' and the search for ‘oligometastasis', ‘oligometastases', ‘oligometastatic', ‘oligometastatic disease' as well as ‘gastric', ‘gastric cancer', ‘stomach', and ‘stomach cancer' yielded very few studies. Most data need to be extrapolated in general studies on oligometastatic diseases of different origins. No randomized controlled trial could be found. Conclusion: In the absence of data to formulate recommendations on how to proceed in the treatment of oligometastatic disease in upper gastrointestinal cancer, a more aggressive treatment of oligometastatic disease can be considered in patients whose tumors show a more favorable neoplastic behavior after the ‘test of time'. The RENAISSANCE study will certainly deliver important data regarding this aspect.

Background To date, patients with metastasized pancreatic ductal adenocarcinoma (PDAC M1) are regarded as a uniform collective. We hypothesize the existence of oligometastatic disease (OMD): a state of PDAC M1 disease with better tumor biology, limited metastasis, and increased survival. Methods Data of 128 PDAC M1 patients treated at the University of Cologne between 2008 and 2018 was reviewed. Interdependence between clinical parameter was calculated using the Mann-Whitney U-Test. Survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. Results Eighty-one (63%) patients had metastases confined to one organ (single organ metastasis, SOG) whereas the remaining 47 (37%) showed multiple metastatic sites (multi-organ metastasis, MOG). Survival analysis revealed a median overall survival (OS) of 12.2 months for SOG vs 4.5 months for MOG (95% CI 5.7–9.8; p p = 0.009). Conclusion We propose a definition of oligometastatic disease in PDAC including anatomical criteria and biological criteria reflecting better tumor biology. The 10 OMD patients (7.8%) survived significantly longer and might even benefit from surgical resection in the future.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Tumor-derived extracellular vesicles (EVs) induce pre-metastatic niche formation to promote metastasis. We isolated EVs from a highly-metastatic pancreatic cancer cell line and patient-derived primary cancer cells by ultracentrifugation. The protein content of EVs was analyzed by mass spectrometry. The effects of PDAC-derived EVs on natural kill (NK) cells were investigated by flow cytometry. The serum EVs&rsquo, TGF-&beta, 1 levels were quantified by ELISA. We found that integrins were enriched in PDAC-derived EVs. The expression of NKG2D, CD107a, TNF-&alpha, and INF-&gamma, in NK cells was significantly downregulated after co-culture with EVs. NK cells also exhibited decreased levels of CD71 and CD98, as well as impaired glucose uptake ability. In addition, NK cell cytotoxicity against pancreatic cancer stem cells was attenuated. Moreover, PDAC-derived EVs induced the phosphorylation of Smad2/3 in NK cells. Serum EVs&rsquo, 1 was significantly increased in PDAC patients. Our findings emphasize the immunosuppressive role of PDAC-derived EVs and provide new insights into our understanding of NK cell dysfunction regarding pre-metastatic niche formation in PDAC.

Magnetic nanoparticles (MNPs) are useful for many biomedical applications, but it is challenging to synthetically produce them in large numbers with uniform properties and surface functionalization. Magnetotactic bacteria (MTB) produce magnetosomes with homogenous sizes, shapes, and magnetic properties. Consequently, there is interest in using MTB as biological factories for MNP production. Nonetheless, MTB can only be grown to low yields, and wild-type strains produce low numbers of MNPs/bacterium. There are also limited technologies to facilitate the selection of MTB with different magnetic contents, such as MTB with compromised and enhanced biomineralization ability. Here, we describe a magnetic microfluidic platform combined with transient cold/alkaline treatment to temporarily reduce the rapid flagellar motion of MTB without compromising their long-term proliferation and biomineralization ability for separating MTB on the basis of their magnetic contents. This strategy enables live MTB to be enriched, which, to the best of our knowledge, has not been achieved with another previously described magnetic microfluidic device that makes use of ferrofluid and heat. Our device also facilitates the high-throughput (25,000 cells/min) separation of wild-type Magnetospirillum gryphiswaldense (MSR-1) from nonmagnetic ΔmamAB MSR-1 mutants with a sensitivity of up to 80% and isolation purity of up to 95%, as confirmed with a gold-standard fluorescent-activated cell sorter (FACS) technique. This offers a 25-fold higher throughput than other previously described magnetic microfluidic platforms (1,000 cells/min). The device can also be used to isolate Magnetospirillum magneticum (AMB-1) mutants with different ranges of magnetosome numbers with efficiencies close to theoretical estimates. We believe this technology will facilitate the magnetic characterization of genetically engineered MTB for a variety of applications, including using MTB for large-scale, controlled MNP production.IMPORTANCE Our magnetic microfluidic technology can greatly facilitate biological applications with magnetotactic bacteria, from selection and screening to analysis. This technology will be of interest to microbiologists, chemists, and bioengineers who are interested in the biomineralization and selection of magnetotactic bacteria (MTB) for applications such as directed evolution and magnetogenetics.

Cancer stem cells (CSCs) have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

Esophageal 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. Between 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. Complete 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. This 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.

Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p

The formation of outer membrane (OM) cytochromes seems to be a key step in the evolution of dissimilatory iron-reducing bacteria. They are believed to be the endpoints of an extended respiratory chain to the surface of the cell that establishes the connection to insoluble electron acceptors such as iron or manganese oxides. The gammaproteobacterium Shewanella oneidensis MR-1 contains the genetic information for five putative OM cytochromes. In this study, the role and specificity of these proteins were investigated. All experiments were conducted using a markerless deletion mutant in all five OM cytochromes that was complemented via the expression of single, plasmid-encoded genes. MtrC and MtrF were shown to be potent reductases of chelated ferric iron, birnessite, and a carbon anode in a microbial fuel cell. OmcA-producing cells were unable to catalyze iron and electrode reduction, although the protein was correctly produced and oriented. However, OmcA production resulted in a higher birnessite reduction rate compared with the mutant. The presence of the decaheme cytochrome SO_2931 as well as the diheme cytochrome SO_1659 did not rescue the phenotype of the deletion mutant.

Owing to their small size and enhanced stability, nanobodies derived from camelids have previously been used for the construction of intracellular “nanotraps,” which enable redirection and manipulation of green fluorescent protein (GFP)-tagged targets within living plant and animal cells. By taking advantage of intracellular compartmentalization in the magnetic bacterium Magnetospirillum gryphiswaldense, we demonstrate that proteins and even entire organelles can be retargeted also within prokaryotic cells by versatile nanotrap technology. Expression of multivalent GFP-binding nanobodies on magnetosomes ectopically recruited the chemotaxis protein CheW1-GFP from polar chemoreceptor clusters to the midcell, resulting in a gradual knockdown of aerotaxis. Conversely, entire magnetosome chains could be redirected from the midcell and tethered to one of the cell poles. Similar approaches could potentially be used for building synthetic cellular structures and targeted protein knockdowns in other bacteria. Importance Intrabodies are commonly used in eukaryotic systems for intracellular analysis and manipulation of proteins within distinct subcellular compartments. In particular, so-called nanobodies have great potential for synthetic biology approaches because they can be expressed easily in heterologous hosts and actively interact with intracellular targets, for instance, by the construction of intracellular “nanotraps” in living animal and plant cells. Although prokaryotic cells also exhibit a considerable degree of intracellular organization, there are few tools available equivalent to the well-established methods used in eukaryotes. Here, we demonstrate the ectopic retargeting and depletion of polar membrane proteins and entire organelles to distinct compartments in a magnetotactic bacterium, resulting in a gradual knockdown of magneto-aerotaxis. This intracellular nanotrap approach has the potential to be applied in other bacteria for building synthetic cellular structures, manipulating protein function, and creating gradual targeted knockdowns. Our findings provide a proof of principle for the universal use of fluorescently tagged proteins as targets for nanotraps to fulfill these tasks., Importance Intrabodies are commonly used in eukaryotic systems for intracellular analysis and manipulation of proteins within distinct subcellular compartments. In particular, so-called nanobodies have great potential for synthetic biology approaches because they can be expressed easily in heterologous hosts and actively interact with intracellular targets, for instance, by the construction of intracellular “nanotraps” in living animal and plant cells. Although prokaryotic cells also exhibit a considerable degree of intracellular organization, there are few tools available equivalent to the well-established methods used in eukaryotes. Here, we demonstrate the ectopic retargeting and depletion of polar membrane proteins and entire organelles to distinct compartments in a magnetotactic bacterium, resulting in a gradual knockdown of magneto-aerotaxis. This intracellular nanotrap approach has the potential to be applied in other bacteria for building synthetic cellular structures, manipulating protein function, and creating gradual targeted knockdowns. Our findings provide a proof of principle for the universal use of fluorescently tagged proteins as targets for nanotraps to fulfill these tasks.

Most motile bacteria navigate within gradients of external chemical stimuli by regulating the length of randomly oriented swimming episodes. Magnetotactic bacteria are characterized by chains of intracellular ferromagnetic nanoparticles and their ability to sense the geomagnetic field, which is believed to facilitate directed motion, but is not well understood at the behavioural and molecular level. Here, we show that cells of Magnetospirillum gryphiswaldense unexpectedly display swimming polarity that depends on aerotactic signal transduction through one of its four chemotaxis operons (cheOp1). Growth of cells in magnetic fields superimposed on oxygen gradients results in a gradual inherited bias of swimming runs with one of the cell poles leading, such that the resulting overall swimming direction of entire populations can be reversed by changes in oxygen concentration. These findings clearly show that there is a direct molecular link between aerotactic sensing and the determination of magnetotactic polarity, through the sensory pathway, CheOp1.

Adipose tissue derived stem cells (ASC) has currently been highly attracted as a new source for regenerative medicine as well as promising avenue of investigation for the delivery of adjuvant therapies in various disease. A criticized standard protocol of generating purified good quality and quantity of ASCs is emergent in need.