Comparison of the collagen haemostat Sangustop(R) versus a carrier-bound fibrin sealant during liver resection; ESSCALIVER-study

Background: Haemostasis in liver surgery remains a challenge despite improved resection techniques. Oozing from blood vessels too small to be ligated necessitate a treatment with haemostats in order to prevent complications attributed to bleeding. There is good evidence from randomised trials for the efficacy of fibrin sealants, on their own or in combination with a carrier material. A new haemostatic device is Sangustop(R). It is a collagen based material without any coagulation factors. Pre-clinical data for Sangustop(R) showed superior haemostatic effect. This present study aims to show that in the clinical situation Sangustop(R) is not inferior to a carrier-bound fibrin sealant (Tachosil(R)) as a haemostatic treatment in hepatic resection. Methods: This is a multi-centre, patient-blinded, intra-operatively randomised controlled trial. A total of 126 patients planned for an elective liver resection will be enrolled in eight surgical centres. The primary objective of this study is to show the non-inferiority of Sangustop(R) versus a carrier-bound fibrin sealant (Tachosil(R)) in achieving haemostasis after hepatic resection. The surgical intervention is standardised with regard to devices and techniques used for resection and primary haemostasis. Patients will be followed-up for three months for complications and adverse events. Discussion: This randomised controlled trial (ESSCALIVER) aims to compare the new collagen haemostat Sangustop(R) with a carrier-bound fibrin sealant which can be seen as a "gold standard" in hepatic and other visceral organ surgery. If non-inferiority is shown other criteria than the haemostatic efficacy (e.g. costs, adverse events rate) may be considered for the choice of the most appropriate treatment. Trial Registration: NCT0091861

Evaluation and metrological performance of a novel ionisation vacuum gauge suitable as reference standard

Funding Information: This work has received funding from the EMPIR programme (projects 16NRM05 and 20SIP01) co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation programme and the Portuguese National Funding Agency for Science, Research and Technology in the framework of the project UIDB/FIS/ 00068/2020. Publisher Copyright: © 2023 The Author(s)Recently, a new type of ionization vacuum gauge was introduced, which was proposed as a reference and transfer standard in the range of 10-6 Pa to 10-2 Pa because of its excellent stability and linearity. In contrast to present models of ionisation vacuum gauges, all electrons have a well-defined path length through the ionisation space. This even allows one to predict the sensitivity for a gas species provided that the ionisation cross section of the gas molecules for electrons between 50 eV and 200 eV is known. Following the development of this gauge we investigated its metrological performance in terms of linearity, resolution, repeatability, reproducibility, transport and long-term stability, disturbances by magnetic fields, influence of the surrounding earth potential and so on. The gauge demonstrated excellent metrological properties and is indeed suitable as an accurate reference and transfer standard, but can also provide important economic benefits to manufacturers and users.publishersversionpublishe

Deposition Order Controls the First Stages of a Metal-Organic Coordination Network on an Insulator Surface

Schüller L, Haapasilta V, Kuhn S, et al. Deposition Order Controls the First Stages of a Metal-Organic Coordination Network on an Insulator Surface. Journal of Physical Chemistry C. 2016;120(27):14730-14735.We report on first stages toward the formation of a surface-confined metal organic coordination network (MOCN) by sequential deposition of biphenyl-4,4'-dicarboxylic acid and iron atoms on the surface of a bulk insulator, calcite (10.4). The influence of the deposition order on the structure formation is studied by noncontact atomic force microscopy operated in ultrahigh vacuum at room temperature. It is found that sequential deposition facilitates MOCN formation when the organic linker molecules are first adsorbed on the surface, followed by iron deposition. This observation is explained by first-principles computations, indicating that the metal molecule interaction dominates over the molecule molecule interaction on the surface. The observed MOCN islands are elongated in the [010] substrate direction, demonstrating a templating effect of the underlying substrate. This experimental finding is confirmed by calculations suggesting that the MOCN network matches the calcite lattice periodicity in the [010] direction but not in the [(42) over bar1] direction. This work, thus, demonstrates the decisive influence of both deposition order and lattice matching on the formation of an extended MOCN on a bulk insulator surface

Diacetylene polymerization on a bulk insulator surface

Richter A, Haapasilta V, Venturini C, et al. Diacetylene polymerization on a bulk insulator surface. Physical Chemistry Chemical Physics. 2017;19(23):15172-15176.Molecular electronics has great potential to surpass known limitations in conventional silicon-based technologies. The development of molecular electronics devices requires reliable strategies for connecting functional molecules by wire-like structures. To this end, diacetylene polymerization has been discussed as a very promising approach for contacting single molecules with a conductive polymer chain. A major challenge for future device fabrication is transferring this method to bulk insulator surfaces, which are mandatory to decouple the electronic structure of the functional molecules from the support surface. Here, we provide experimental evidence for diacetylene polymerization of 3,30-(1,3-butadiyne-1,4-diyl) bisbenzoic acid precursors on the (10.4) surface of calcite, a bulk insulator with a band gap of around 6 eV. When deposited on the surface held at room temperature, ordered islands with a (1 x 3) superstructure are observed using dynamic atomic force microscopy. A distinct change is revealed upon heating the substrate to 485 K. After heating, molecular stripes with a characteristic inner structure are formed that excellently match the expected diacetylene polymer chains in appearance and repeat distance. The corresponding density functional theory computations reveal molecular-level bonding patterns of both the (1 x 3) superstructure and the formed striped structure, confirming the assignment of on-surface diacetylene polymerization. Transferring the concept of using diacetylene polymerization for creating conductive connections to bulk insulator surfaces paves the way towards application-relevant systems for future molecular electronic devices

The weight function for charges-A rigorous theoretical concept for Kelvin probe force microscopy

Söngen H, Rahe P, Neff JL, et al. The weight function for charges-A rigorous theoretical concept for Kelvin probe force microscopy. Journal of Applied Physics. 2016;119(2):25304.A comprehensive discussion of the physical origins of Kelvin probe force microscopy (KPFM) signals for charged systems is given. We extend the existing descriptions by including the openloop operation mode, which is relevant when performing KPFM in electrolyte solutions. We define the contribution of charges to the KPFM signal by a weight function, which depends on the electric potential and on the capacitance of the tip-sample system. We analyze the sign as well as the lateral decay of this weight function for different sample types, namely, conductive samples as well as dielectric samples with permittivities both larger and smaller than the permittivity of the surrounding medium. Depending on the surrounding medium the sign of the weight function can be positive or negative, which can lead to a contrast inversion for single charges. We furthermore demonstrate that the KPFM signal on thick dielectric samples can scale with the sample size-rendering quantitative statements regarding the charge density challenging. Thus, knowledge on the weight function for charges is crucial for qualitative as well as quantitative statements regarding charges beneath the tip. (C) 2016 AIP Publishing LLC

Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial

IMPORTANCE: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. RESULTS: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. CONCLUSIONS AND RELEVANCE: Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00849615.info:eu-repo/semantics/publishedVersio

Hydration layers at the graphite-water interface: Attraction or confinement

Söngen H, Morais Jaques Y, Zivanovic L, et al. Hydration layers at the graphite-water interface: Attraction or confinement. Physical Review B. 2019;100(20):205410

Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European liver transplant registry

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data

Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

BACKGROUND: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. METHODS: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n  38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. RESULTS: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. CONCLUSIONS: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases

Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial

Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient’s liver metastases as surgically removable. Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11⋅9 per cent) and control (25, 11⋅0 per cent) arms (P = 0⋅775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33⋅7 per cent) versus 54 of 472 (11⋅4 per cent) respectively (P = 0⋅001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38⋅1 per cent) versus 66 of 228 (28⋅9 per cent) respectively (P < 0⋅001). Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM