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Double-walled carbon nanotube-yttria-stabilized ZrO2 nanocomposites are prepared by a mixing route followed by Spark Plasma Sintering. The double-walled carbon nanotubes (DWCNTs) have been previously subjected to a covalent functionalization. The nanocomposites present a high densification and show a homogenous dispersion of DWCNTs into a matrix about 100 nm in size. The DWCNTs are well distributed at the matrix grain boundaries but form larger bundles upon the increase in carbon content. The Vickers microhardness of the nanocomposites decreases regularly upon the increase in carbon content. Incorporation of carbon at contents higher than 2 wt.% results in significantly lower friction coefficients, both against alumina and steel balls, possibly because of the elastic deformation of the DWCNTs at the surface of the sample. Their presence also favors a reduction of the steel/ceramic contacts and reduces the wear of the steel ball at high loads. DWCNTs improve wear resistance and reduce friction without incurring any severe damage, contrary to multi-walled carbon nanotubes.

Summary: Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral or non-viral etiologies including steatotic liver diseases (SLDs). Expansion of immunosuppressive myeloid cells is a hallmark of inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance. Here, we present a high-resolution atlas of innate immune cells from patients with HCC that unravels an SLD-associated contexture characterized by influx of inflammatory and immunosuppressive myeloid cells, including a discrete population of THBS1+ regulatory myeloid (Mreg) cells expressing monocyte- and neutrophil-affiliated genes. THBS1+ Mreg cells expand in SLD-associated HCC, populate fibrotic lesions, and are associated with poor prognosis. THBS1+ Mreg cells are CD163+ but distinguished from macrophages by high expression of triggering receptor expressed on myeloid cells 1 (TREM1), which contributes to their immunosuppressive activity and promotes HCC tumor growth in vivo. Our data support myeloid subset-targeted immunotherapies to treat HCC.

The aim is to prepare Fe–Al2O3 ceramic-matrix composites with a high Fe content in order to benefit from a high degree of toughening. Fe–Al2O3 powders with different Fe contents (14.2–47.4 vol%) are prepared by selective reduction in H2 of the corresponding amorphous Al2-2xFe2xO3 oxides, themselves prepared by decomposition in air of the mixed oxalates. Dense samples are prepared by Spark Plasma Sintering. The samples are investigated by thermal analysis, scanning electron microscopy and X-ray diffraction. The microhardness, fracture strength and toughness are discussed with respect to the composition and the microstructure, i.e. a dispersion of discrete Fe particles or a continuous Fe network into the alumina matrix. The latter samples are significantly thougher than the former ones (about 14 and 8 MPa m1/2, respectively).

Abstract Pancreatic ductal adenocarcinoma (PDAC) patients eligible for curative surgery undergo unpredictable disease relapse. Even patients with a good pathological response after neoadjuvant treatment (NAT) remain susceptible to recurrent PDAC. Molecular analysis of R0 margins may identify patients with a worse prognosis. The molecular status of mutant KRAS (exon 2, codon 12/13) was analysed retrospectively by digital droplet PCR in tumour areas, venous and resection margins of resected tumours, either undergoing up-front surgery (UFS) or after NAT with a good pathological response. Expectedly, tumour tissues or remnants from patients who underwent NAT presented lower KRAS mutant allele frequencies (MAF) than patients eligible for UFS. Similarly, ypT1 tumour MAFs were greater than the ypT0 tumour remnant MAFs in the NAT group. Mutant KRAS status in margins did not distinguish NAT subgroups. It was not predictive of shorter recurrence-free or overall survival within or between groups. KRAS-double negativity in both venous and resection margins did not identify patients with a better prognosis, regardless of the groups. The cohorts ‘sizes were small due to limited numbers of patients meeting the inclusion criteria, but KRAS-positivity or MAFs in resection and venous margins did not carry prognostic value. Comparison of margins from good versus bad responders receiving NAT may provide better clinical value.

Abstract Background CAPARFI study explored whether sonoelastographic data collected using the acoustic radiation force impulse (ARFI) system are reliable when evaluating skeletal muscles and whether the technique can detect muscle changes with aging. Methods Twenty young (YH; 18–30 years) and 30 old (OH; ≥70 years) healthy volunteers and 15 old patients with cancer (OP; ≥70 years) were assessed through quantitative ARFI measurements (m s−1) of the relaxed rectus femoris, tibialis anterior, and soleus muscles, and Short Physical Performance Battery (SPPB) test. The reliability in ARFI measurements was evaluated by intra‐class correlation coefficient. Among‐group differences in ARFI measurements and SPPB were evaluated using a global linear model. Results Acoustic radiation force impulse measurements demonstrated high reliability in all groups (intra‐class correlation coefficient > 0.82). ARFI measurements of the rectus femoris muscle were significantly lower in both the OH and OP groups than in the YH group (1.46 ± 0.12 and 1.50 ± 0.32 vs. 1.80 ± 0.35 m s−1). The ARFI measurements of the soleus muscle were significantly lower in the OP group than in the YH group (1.37 ± 0.37 vs. 1.70 ± 0.53 m s−1). No significant difference was observed for tibialis anterior muscle. Significantly lower SPPB scores were observed in the OP group (10.3 ± 1.4 out of 12) than in the YH (12.0 ± 0.0) and OH groups (11.5 ± 1.0). Conclusions This study demonstrated that ARFI quantitative measurements are reliable in relaxed skeletal muscle and may be reliably used to explore muscle changes with aging and/or neoplasia in clinical practice.

Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico‐pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis.

Abstract Background In patients undergoing major liver resection, portal vein embolization (PVE) has been widely used to induce hypertrophy of the non-embolized liver in order to prevent post-hepatectomy liver failure. PVE is a safe and effective procedure, but does not always lead to sufficient hypertrophy of the future liver remnant (FLR). Hepatic vein(s) embolization has been proposed to improve FLR regeneration when insufficient after PVE. The sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FLR but it implies two different procedures with no time gain as compared to PVE alone. We have developed the so-called liver venous deprivation (LVD), a combination of PVE and HVE during the same intervention, to optimize the phase of liver preparation before surgery. The main objective of this randomized phase II trial is to compare the percentage of change in FLR volume at 3 weeks after LVD or PVE. Methods Patients eligible to this multicenter prospective randomized phase II study are subjects aged from 18 years old suffering from colo-rectal liver metastases considered as resectable and with non-cirrhotic liver parenchyma. The primary objective is the percentage of change in FLR volume at 3 weeks after LVD or PVE using MRI or CT-Scan. Secondary objectives are assessment of tolerance, post-operative morbidity and mortality, post-hepatectomy liver failure, rate of non-respectability due to insufficient FLR or tumor progression, per-operative difficulties, blood loss, R0 resection rate, post-operative liver volume and overall survival. Objectives of translational research studies are evaluation of pre- and post-operative liver function and determination of biomarkers predictive of liver hypertrophy. Sixty-four patients will be included (randomization ratio 1:1) to detect a difference of 12% at 21 days in FLR volumes between PVE and LVD. Discussion Adding HVE to PVE during the same procedure is an innovative and promising approach that may lead to a rapid and major increase in volume and function of the FLR, thereby increasing the rate of resectable patients and limiting the risk of patient’s drop-out. Trial registration This study was registered on clinicaltrials.gov on 15th February 2019 ( NCT03841305 ).

Abstract Background Approximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10–15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low (

The reuse of industrial waste, such as electric arc furnace dust (EAFD) as reinforcement in aluminum matrix composites (AMC), is still little explored even though it has shown potential to improve the mechanical properties, such as hardness and mechanical strength, of AMCs. To propose a new alternative for EAFD recycling, AA7075-EAFD composites were produced by spark plasma sintering (SPS). The starting powders were prepared by high-energy milling with different weight fractions of EAFD in two particle size ranges added to an AA7075 matrix. SEM shows that the distribution of reinforcement particles in the matrix is homogeneous with no agglomeration of the particles. XRD patterns of initial powders and the SPS-sintered (SPSed) samples suggest that there was no reaction during sintering (no additional peaks were detected). The relative density of all SPSed samples exceeded 96.5%. The Vickers microhardness of the composites tended to increase with increasing EAFD content, increasing from 108 HV (AA7075 without reinforcement) up to 168 HV (56% increase). The maximum microhardness value was obtained when using 15 wt.% EAFD with a particle size smaller than 53 μm (called G1), showing that EAFD presents a promising potential to be applied as reinforcement in AA7075 matrix composites.

Tumor-released extracellular vesicles (EVs) contain tumor-specific cargo distinguishing them from healthy EVs, and making them eligible as circulating biomarkers. Glypican 1 (GPC1)-positive exosome relevance as liquid biopsy elements is still debated. We carried out a prospective study to quantify GPC1-positive exosomes in sera from pancreatic ductal adenocarcinoma (PDAC) patients undergoing up-front surgery, as compared to controls including patients without cancer history and patients displaying pancreatic preneoplasic lesions. Sera were enriched in EVs, and exosomes were pulled down with anti-CD63 coupled magnetic beads. GPC1-positive bead percentages determined by flow cytometry were significantly higher in PDAC than in the control group. Diagnosis accuracy reached 78% (sensitivity 64% and specificity 90%), when results from peripheral and portal blood were combined. In association with echo-guided-ultrasound-fine-needle-aspiration (EUS-FNA) negative predictive value was 80% as compared to 33% for EUS-FNA only. This approach is clinically relevant as a companion test to the already available diagnostic tools, since patients with GPC1-positive exosomes in peripheral blood showed decreased tumor free survival.

Circulating tumor cell (CTC) detection and numeration are becoming part of the common clinical practice, especially for breast, colon, and prostate cancer. However, their paucity in peripheral blood samples is an obstacle for their identification. Several groups have tried to improve CTC recovery rate by developing highly sensitive cellular and molecular detection methods. However, CTCs are still difficult to detect in peripheral blood. Therefore, their recovery rate could be increased by obtaining blood samples from vessels close to the drainage territories of the invaded organ, when the anatomical situation is favorable. This approach has been tested mostly during tumor resection surgery, when the vessels nearest to the tumor are easily accessible. Moreover, radiological (including echo‐guided based and endovascular techniques) and/or endoscopic routes could be utilized to obtain CTC samples close to the tumor in a less invasive way than conventional biopsies. The purpose of this article is to summarize the available knowledge on CTC recovery from blood samples collected close to the tumor (i.e., in vessels located in the drainage area of the primary tumor or metastases). The relevance of such an approach for diagnostic and prognostic evaluations will be discussed, particularly for pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and non‐small‐cell lung cancer.

Abstract Background The European Consensus 2018 established a new algorithm with absolute and relative criteria for intraductal papillary mucinous neoplasms of the pancreas (IPMN) management. The aim of this study was to validate these criteria and analyse the outcomes in function of the surgical procedure and IPMN subtype. Methods Clinical, radiological and surgical data (procedure, morbidity/mortality rates) of patients who underwent surgery for IPMN between 2007 and 2017. The predictive value of the different criteria was analysed. Results 124 patients (men 67%; mean age 65 years) underwent surgery for IPMN (n = 62 malignant tumours; 50%). Jaundice, cyst ≥4 cm and Wirsung duct size 5–9.9 mm or ≥ 10 mm were significantly associated with malignancy (4.77

Abstract Background Older adults with cancer experience negative long‐term functional effects of both cancer and treatments. Exercise may minimize their age‐related and cancer‐related functional decline. Methods We conducted a multicentre open‐label 12 month randomized clinical trial with two parallel arms including participants aged ≥70 years with lymphoma or carcinoma requiring curative treatment. The study started at the beginning of any phase of cancer treatment (surgery, chemotherapy, or radiotherapy). The usual care group (UCG) received the current national recommendations in physical activity (a guideline without specific counselling). The intervention group (IG) received 1 year phoned physical activity advice individually adapted to physical assessment (twice a month during the first 6 months and then monthly). The primary outcome was the proportion of subjects with a 1 year decreased short physical performance battery (SPPB) score of 1 point or more. Physical, cognitive, and clinical secondary outcomes were also investigated. Results We allocated 301 participants (age 76.7 ± 5.0, female 60.6%) to each group. At baseline, the median SPPB was 10/12 in both groups. Breast was the most frequent tumour site (35.7%). After 1 year, 14.0% of participants in the UCG and 18.7% in the IG had a decrease in SPPB score of 1 point or more (P = 0.772). At 2 years, there was no difference in SPPB, gait speed, International Physical Activity Questionnaire score, and verbal fluency. Subgroup analyses after 2 years showed a decline in SPPB for 29.8% of UCG and 5.0% of IG breast cancer participants (P = 0.006), in 21.7% of UCG and 6.2% of IG female participants (P = 0.019), and in 24.5% of UCG and 11.1% of IG normal nutritional status participants (P = 0.009). Falls, hospitalization, institutionalization, and death rates were similar in both groups. Conclusions Personalized phoned physical activity advice had not reduced functional decline at 1 year but provided preliminary evidence that may prevent physical performance decline at 2 years in older adults with breast cancer.

Extracellular vesicles (EVs) are produced by healthy tissues and tumor cells and are released in various bodily fluids, including blood. They are limited by bilayer phospholipidic membranes, and they carry a rich content in biomolecules. Their release cleanses the cells of their waste or serves as functional local and distant cell–cell communication and molecular exchange particles. This rich and heterogeneous content has been given intense attention in cancer physiopathology because EVs support cancer control and progression. Because of their specific active cargo, they are being evaluated as carriers of liquid biopsy biomarkers. Compared to soluble circulating biomarkers, their complexity might provide rich information on tumor and metastases status. Thanks to the acquired genomic changes commonly observed in oncogenic processes, double-stranded DNA (dsDNA) in EVs might be the latest most promising biomarker of tumor presence and complexity. This review will focus on the recent knowledge on the DNA inclusion in vesicles, the technical aspects of EV-DNA detection and quantification, and the use of EV-DNA as a clinical biomarker.

Abstract Background The majority of patients undergoing hepatectomy for hepatocellular carcinoma (HCC) suffer from underlying liver disease and are exposed to the risk of postoperative ascites, which is favored by an imbalance between portal venous inflow and a diminished hepatic volume. Finding a reversible, non-invasive method for modulating the portal inflow would be of interest as it could be used temporarily during the early postoperative course. Somatostatin, a well-known drug already used in several indications, may limit the risk of postoperative ascites and liver failure by decreasing portal pressure after hepatectomy for HCC in patients with underlying liver disease. We aimed to evaluate the impact of somatostatin postoperative infusion on the incidence of ascites following hepatectomy by laparotomy for HCC in patients with underlying liver disease. Methods/design The SOMAPROTECT study is a multicenter randomized double-blind placebo controlled phase III trial comparing two arms of patients with underlying liver disease undergoing hepatectomy for HCC by open approach. All patients will have primary abdominal drainage before closure. Patients in the experimental arm will receive a postoperative intravenous infusion of somatostatin during 6 days. Patients in the control group will receive a placebo infusion for the same duration. The primary endpoint will be the presence or absence of postoperative ascites occurring during the 90-day postoperative course, defined as ≥500 ml/24 h of fluid in the drains during at least 3 days or any ascites requiring an invasive procedure comprising percutaneous puncture or drainage. Secondary endpoints will be duration and total volume of ascites, postoperative 90-day mortality and morbidity, liver failure, acute renal failure, length of stay in intensive care unit and hospital stay. The total number of patients to be enrolled was calculated to be 152. Discussion Postoperative ascites remains a major issue after hepatectomy for HCC as it is associated with increased morbidity, liver and renal failure, the need for specific treatments and prolonged hospital stay. This study represents the first randomized controlled trial to assess the benefits of somatostatin on the risk of postoperative ascites after surgery for HCC. Trial registration NCT02799212 (ClinicalTrials.gov identifier). Registered prior to conducting the research on 9 June 2016.

The purpose of the ForM@Ter LArge-scale multi-Temporal Sentinel-1 InterferoMetry service (FLATSIM) is the massive processing of Sentinel-1 data using multi-temporal interferometric synthetic aperture radar (InSAR) over large areas, i.e., greater than 250,000 km2. It provides the French ForM@ter scientific community with automatically processed products using a state of the art processing chain based on a small baseline subset approach, namely the New Small Baseline (NSBAS). The service results from a collaboration between the scientific team that develops and maintains the NSBAS processing chain and the French Spatial Agency (CNES) that mirrors the Sentinel-1 data. The proximity to Sentinel-1 data, the NSBAS workflow, and the specific optimizations to make NSBAS processing massively parallel for the CNES high performance computing infrastructure ensures the efficiency of the chain, especially in terms of input and output, which is the key for the success of such a service. The FLATSIM service is made of a production module, a delivery module and a user access module. Products include interferograms, surface line of sight velocity, phase delay time series and auxiliary data. Numerous quality indicators are provided for an in-depth analysis of the quality and limits of the results. The first national call in 2020 for region of interest ended up with 8 regions spread over the world with scientific interests, including seismology, tectonics, volcano-tectonics, and hydrological cycle. To illustrate the FLATSIM capabilities, an analysis is shown here on two processed regions, the Afar region in Ethiopa, and the eastern border of the Tibetan Plateau.

AA7075 aluminum alloy is widely used for several high-technology applications for its high mechanical strength to weight ratio but is still the subject of several studies seeking a further increase in its mechanical properties. A commercial powder is used, either as-received or after ball-milling. Dense AA7075 samples are prepared in one step by Spark Plasma Sintering, at 550 °C with a holding time of 15 min and a uniaxial pressure of 100 MPa. No additional heat treatment is performed. Laser granulometry, X-ray diffraction and optical- and scanning electron microscopy show that both grain size and morphology are preserved in the dense samples, due to the relatively low temperature and short sintering time used. The samples prepared using the ball-milled powder exhibit both higher Vickers microhardness and transverse fracture strength values than those prepared using the raw powder, reflecting the finer microstructure.

We present five cases in whom two rare entities were simultaneously found within the liver, i.e. hepatocellular adenomas (HCAs) and granulomas. Coexistence of both entities confuses diagnosis. Our aim is to disclose the association between HCA and hepatic granulomas. Five patients presented with HCA for which they underwent resection. During laparotomy or at pathological examination, granulomas were found in tumorous and non-tumorous tissue. No specific cause for the granulomas was found. Immunohistochemistry showed overexpression of C-reactive protein and serum amyloid A in 4/5 patients, classifying these lesions as inflammatory HCA. HCA and especially the inflammatory subtype may cause formation of granulomas in (peri-)tumorous tissue as a local response to persistent inflammation and/or the presence of a tumor. Both HCA and hepatic granulomas have also been associated with oral contraceptive use. In conclusion, HCAs associated with hepatic granulomas derive from a local response to (inflammatory) HCA or neoplasm, chronic use of oral contraceptives, or a combination of these factors.

In Europe and North America, hepatocellular adenomas (HCA) occur, classically, in middle-aged woman taking oral contraceptives. Twenty percent of women, however, are not exposed to oral contraceptives; HCA can more rarely occur in men, children, and women over 65 years. HCA have been observed in many pathological conditions such as glycogenosis, familial adenomatous polyposis, MODY3, after male hormone administration, and in vascular diseases. Obesity is frequent particularly in inflammatory HCA. The background liver is often normal, but steatosis is a frequent finding particularly in inflammatory HCA. The diagnosis of HCA is more difficult when the background liver is fibrotic, notably in vascular diseases. HCA can be solitary, or multiple or in great number (adenomatosis). When nodules are multiple, they are usually of the same subtype. HNF1α-inactivated HCA occur almost exclusively in woman. The most important point of the classification is the identification of β-catenin mutated HCA, a strong argument to identify patients at risk of malignant transformation. Some HCA already present criteria indicating malignant transformation. When the whole nodule is a hepatocellular carcinoma, it is extremely difficult to prove that it is the consequence of a former HCA. It is occasionally difficult to identify HCA remodeled by necrosis or hemorrhage.