Minimally invasive versus open distal pancreatectomy for resectable pancreatic neuroendocrine tumors: A propensity score matched multicentric comparative French study.

BACKGROUND: Minimally invasive surgery has gained momentum for left pancreatic resections. However, debate remains about whether it has any advantage over open surgery for distal pancreatectomy for pancreatic neuroendocrine tumors. METHODS: This retrospective review examined pancreatectomies performed for resectable pancreatic neuroendocrine tumors at 21 centers in France between January 2014 and December 2018. Short and long-term outcomes were compared before and after propensity score matching based on tumor size, sex, age, body mass index, center, and method of pancreatic transection. RESULTS: During the period study, 274 patients underwent left pancreatic resection for pancreatic neuroendocrine tumors [109 underwent distal splenopancreatectomy, and 165 underwent spleen-preserving distal pancreatectomy [(splenic vessel preservation (n = 97; 58.7%)/splenic vessel resection (n = 68; 41.3%)]. Before propensity score matching, minimally invasive surgery was associated with a lower rate of major morbidity (P = .004), lower rate of postoperative delayed gastric emptying (P = .04), and higher rate of "textbook" outcomes (P = .04). After propensity score matching, there were 2 groups of 54 patients (n = 30 distal splenopancreatectomy; n = 78 spleen-preserving distal pancreatectomy). Minimally invasive surgery was associated with less blood loss (P = .05), decreased rate of major morbidity (6% vs. 24%; P = .02), less delayed gastric emptying (P = .05) despite similar rates of postoperative fistula, hemorrhage, and reoperation (P > .05). The 5-year overall survival (79% vs. 75%; P = .74) and recurrence-free survival (10% vs 17%; P = .39) were similar. CONCLUSION: Minimally invasive surgery for left pancreatic resection can be safely proposed for patients with resectable left pancreatic neuroendocrine tumors. Minimally invasive surgery decreases the rate of major complications while providing comparable long-term oncologic outcomes.

The impact of cirrhosis on short and long postoperative outcomes after distal pancreatectomy.

BACKGROUND: The impact of cirrhosis on the postoperative outcomes of distal pancreatectomy is yet to be reported. We aimed to evaluate the outcomes of distal pancreatectomy in patients with cirrhosis. METHODS: We conducted a retrospective, multicentric study patients with cirrhosis who underwent planned distal pancreatectomy between 2008 and 2020 in French high volume centers. Patients with cirrhosis were matched 1:4 for demographic, surgical, and histologic criteria with patients without cirrhosis. The primary endpoint was severe morbidity (Clavien-Dindo grade ≥III). The secondary endpoints were postoperative complications, specifically related to cirrhosis and pancreatic surgery, and survival for patients with pancreatic adenocarcinoma. RESULTS: Overall, 32 patients with cirrhosis were matched with 128 patients without cirrhosis. Most patients (93.5%) had Child-Pugh A cirrhosis. The severe morbidity rate after distal pancreatectomy was higher in patients with cirrhosis than in those without cirrhosis (28.13% vs 25.75%, P = .11. The operative time was significantly longer in the cirrhotic group compared with controls (P = .01). However, patients with and without cirrhosis had comparable blood loss and conversion rates. Postoperatively, the two groups had similar rates of pancreatic fistula, hemorrhage, reoperation, postoperative mortality, and survival rates at 1, 3, and 5 years. CONCLUSION: The current study suggests that distal pancreatectomy in high-volume centers is feasible for patients with compensated cirrhosis.

Droplet digital polymerase chain reaction detection of KRAS mutations in pancreatic FNA samples: Technical and practical aspects for routine clinical implementation.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is associated with a 5-year survival rate of less than 6%, and current treatments have limited efficacy. The diagnosis of PDAC is mainly based on a cytologic analysis of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples. However, the collected specimens may prove noncontributory in a significant number of cases, delaying patient management and treatment. The combination of EUS-FNA sample examination and KRAS mutation detection can improve the sensitivity for diagnosis. In this context, the material used for molecular analysis may condition performance. METHODS: The authors prospectively compared the performance of cytologic analysis combined with a KRAS droplet digital polymerase chain reaction (ddPCR) assay for PDAC diagnosis using either conventional formalin-fixed, paraffin-embedded cytologic samples or needle-rinsing fluids. RESULTS: Molecular testing of formalin-fixed, paraffin-embedded cytologic samples was easier to set up, but the authors observed that the treatment of preanalytic samples, in particular the fixation process, drastically reduced ddPCR sensitivity, increasing the risk of false-negative results. Conversely, the analysis of dedicated, fresh needle-rinsing fluid samples appeared to be ideal for ddPCR analysis; it had greater sensitivity and was easily to implement in clinical use. In particular, fluid collection by the endoscopist, transportation to the laboratory, and subsequent freezing did not affect DNA quantity or quality. Moreover, the addition of KRAS mutation detection to cytologic examination improved diagnosis performance, regardless of the source of the sample. CONCLUSIONS: Considering all of these aspects, the authors propose the use of an integrated flowchart for the KRAS molecular testing of EUS-FNA samples in clinical routine.

THBS1+ myeloid cells expand in SLD hepatocellular carcinoma and contribute to immunosuppression and unfavorable prognosis through TREM1.

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.

Long-term outcomes after surgical resection of pancreatic metastases from renal Clear-cell carcinoma.

BACKGROUND: Clear-cell renal cell carcinoma frequently metastasizes to the pancreas (PMRCC). The management of such metastases remains controversial due to their frequent multifocality and indolent evolution. METHODS: This study describes the surgical management of these lesions and their long-term oncological outcomes. The study included patients who underwent pancreatic resection of PMRCC at Bordeaux University Hospital between June 2005 and March 2022. Morbidity and mortality were assessed at 90 days. Overall survival (OS) and disease-free (DFS) survival were assessed at 5 years. RESULTS: Forty-two patients underwent pancreatic resection for PMRCC, including 18 (42.8 %) total pancreatectomies. The median time from nephrectomy to the diagnosis of PMRCC was 121 (range: 6-400) months. Lesions were multiple in 19/42 (45.2 %) patients. Ten (23.8 %) patients suffered a severe complication (Dindo-Clavien classification ≥ IIIA by D90), including one patient who died postoperatively. The median follow-up was 76 months. The R0 rate was 100 %. The OS and DFS rates were 92.8 % and 29.6 %, respectively, at 5 years. CONCLUSION: Pancreatic resection for PMRCC provides long-term oncological control despite a high recurrence rate.

Management and outcomes of hemorrhage after distal pancreatectomy: a multicenter study at high volume centers.

BACKGROUND: Data on clinically relevant post-pancreatectomy hemorrhage (CR-PPH) are derived from series mostly focused on pancreatoduodenectomy, and data after distal pancreatectomy (DP) are scarce. METHODS: All non-extended DP performed from 2014 to 2018 were included. CR-PPH encompassed grade B and C PPH. Risk factors, management, and outcomes of CR-PPH were evaluated. RESULTS: Overall, 1188 patients were included, of which 561 (47.2 %) were operated on minimally invasively. Spleen-preserving DP was performed in 574 patients (48.4 %). Ninety-day mortality, severe morbidity and CR-POPF rates were 1.1 % (n = 13), 17.4 % (n = 196) and 15.5 % (n = 115), respectively. After a median interval of 8 days (range, 0-37), 65 patients (5.5 %) developed CR-PPH, including 28 grade B and 37 grade C. Reintervention was required in 57 patients (87.7 %). CR-PPH was associated with a significant increase of 90-day mortality, morbidity and hospital stay (p < 0.001). Upon multivariable analysis, prolonged operative time and co-existing POPF were independently associated with CR-PPH (p < 0.005) while a chronic use of antithrombotic agent trended towards an increase of CR-PPH (p = 0.081). As compared to CR-POPF, the failure-to-rescue rate in patients who developed CR-PPH was significantly higher (13.8 % vs. 1.3 %, p < 0.001). CONCLUSION: CR-PPH after DP remains rare but significantly associated with an increased risk of 90-day mortality and failure-to-rescue.

Spark plasma sintered catalytic nickel-copper alloy and carbon nanotube electrodes for the hydrogen evolution reaction.

We report the proof-of-concept of spark plasma sintered (SPS) consolidated mesoporous composite catalytic electrodes based on nickel-copper alloys and carbon nanotubes for the electrocatalytic hydrogen evolution reaction (HER) in alkaline media. The optimized electrode (203 m2 g-1, 5 wt% Ni75Cu25) operated at -0.1 A cm-2 (current of -0.15 A) for 24 h with a stable overpotential of about 0.3 V. This newly described freestanding SPS approach allows the rational control of specific surface area, metal loading, and electrocatalytic performance, thus opening a new route to catalytic electrodes with controllable physical and catalytic properties.

Waiting for bile duct dilation before repair of bile duct injury: a worthwhile strategy?

BACKGROUND: Hepaticojejunostomy (HJ) is the gold standard procedure for repairing major bile duct injury (BDI). Dilation status of the BD before repair has not been assessed as a risk factor for anastomotic stricture. METHOD: This retrospective single-centre study was performed on a population of 87 patients with BDI repaired by HJ between 2007 and 2021. Dilation status was assessed preoperatively, and dilation was defined as the presence of visible peripheral intrahepatic BDs with remaining BD diameter > 8 mm. The short- and long-term outcomes of HJ were assessed according to preoperative dilation status. RESULTS: Before final repair, the BDs were dilated (dBD) in 56.3% of patients and not dilated (ND) in 43.7%. Patients with ND at the time of repair had more severe BDI injury than those with dBD (94.7% vs. 77.6%, p = 0.026). The rate of preoperative cholangitis was lower in patients with ND than in those with dBD (10.5% vs. 44.9%, p = 0.001). The rate of short-term morbidity after HJ was 33.3% (ND vs. dBD: 38.8% vs. 26.3%, p = 0.32). Long-term anastomotic stricture rate was 5.7% with a mean follow-up period of 61.3 months. There were no differences in long-term biliary complications according to dilation status (ND vs. dBD: 12.2% vs. 10.5%, p = 1). CONCLUSION: Dilation status of the BD before HJ for BDI seemed to have no impact on short- or long-term outcomes. Both surgical and radiological external biliary drainages after BDI appear to be acceptable options to reduce cholangitis before repair without increasing risk for long-term anastomotic stricture.

Interdomain Linker of the Bioelecrocatalyst Cellobiose Dehydrogenase Governs the Electron Transfer.

Direct bioelectrocatalysis applied in biosensors, biofuel cells, and bioelectrosynthesis is based on an efficient electron transfer between enzymes and electrodes in the absence of redox mediators. Some oxidoreductases are capable of direct electron transfer (DET), while others achieve the enzyme to electrode electron transfer (ET) by employing an electron-transferring domain. Cellobiose dehydrogenase (CDH) is the most-studied multidomain bioelectrocatalyst and features a catalytic flavodehydrogenase domain and a mobile, electron-transferring cytochrome domain connected by a flexible linker. The ET to the physiological redox partner lytic polysaccharide monooxygenase or, ex vivo, electrodes depends on the flexibility of the electron transferring domain and its connecting linker, but the regulatory mechanism is little understood. Studying the linker sequences of currently characterized CDH classes we observed that the inner, mobile linker sequence is flanked by two outer linker regions that are in close contact with the adjacent domain. A function-based definition of the linker region in CDH is proposed and has been verified by rationally designed variants of Neurospora crassa CDH. The effect of linker length and its domain attachment on electron transfer rates has been determined by biochemical and electrochemical methods, while distances between the domains of CDH variants were computed. This study elucidates the regulatory mechanism of the interdomain linker on electron transfer by determining the minimum linker length, observing the effects of elongated linkers, and testing the covalent stabilization of a linker part to the flavodehydrogenase domain. The evolutionary guided, rational design of the interdomain linker provides a strategy to optimize electron transfer rates in multidomain enzymes and maximize their bioelectrocatalytic performance.

Preemptive wirsungostomy: a safe fistula for avoiding a dreadful fistula in elective or planned pancreatoduodenectomy.

BACKGROUND: High-risk pancreatic anastomosis can lead to a high mortality rate after PD due to the development of postoperative pancreatic fistula (POPF). Performing a wirsungostomy by externalizing the pancreatic duct is a poorly known alternative to anastomosis which could reduce the risk of POPF and the associated severe morbidity METHODS: We retrospectively evaluated patients who underwent primary wirsungostomy with PD from January 2007 to December 2021 in our tertiary referral center. Rates of morbidity and mortality with long-term pancreatic functions were studied. RESULTS: Sixty patients were included. The median Updated Alternative Fistula Risk Score (ua-FRS) was 52%, with 95% patients in the high-risk ua-FRS category and 88.3% patients with stage D risk of developing POPF according to the classification of the ISGPS. The mortality rate was 3.3%, and overall 90-day postoperative morbidity was 63.7% with 50% of patients developing major complications. Mean follow-up was 29.8 months. Twelve patients (20%) became diabetic and 35 patients (58.3%) had preserved pancreatic endocrine function CONCLUSION: Preemptive wirsungostomy with PD could be an appropriate procedure for patients with high-risk pancreatic anastomosis. The high associated morbidity could be compromised by the low mortality and preservation of endocrine function compared to total pancreatectomy or severe POPF.

AA16 Oxidoreductases Boost Cellulose-Active AA9 Lytic Polysaccharide Monooxygenases from Myceliophthora thermophila.

Copper-dependent lytic polysaccharide monooxygenases (LPMOs) classified in Auxiliary Activity (AA) families are considered indispensable as synergistic partners for cellulolytic enzymes to saccharify recalcitrant lignocellulosic plant biomass. In this study, we characterized two fungal oxidoreductases from the new AA16 family. We found that MtAA16A from Myceliophthora thermophila and AnAA16A from Aspergillus nidulans did not catalyze the oxidative cleavage of oligo- and polysaccharides. Indeed, the MtAA16A crystal structure showed a fairly LPMO-typical histidine brace active site, but the cellulose-acting LPMO-typical flat aromatic surface parallel to the histidine brace region was lacking. Further, we showed that both AA16 proteins are able to oxidize low-molecular-weight reductants to produce H2O2. The oxidase activity of the AA16s substantially boosted cellulose degradation by four AA9 LPMOs from M. thermophila (MtLPMO9s) but not by three AA9 LPMOs from Neurospora crassa (NcLPMO9s). The interplay with MtLPMO9s is explained by the H2O2-producing capability of the AA16s, which, in the presence of cellulose, allows the MtLPMO9s to optimally drive their peroxygenase activity. Replacement of MtAA16A by glucose oxidase (AnGOX) with the same H2O2-producing activity could only achieve less than 50% of the boosting effect achieved by MtAA16A, and earlier MtLPMO9B inactivation (6 h) was observed. To explain these results, we hypothesized that the delivery of AA16-produced H2O2 to the MtLPMO9s is facilitated by protein-protein interaction. Our findings provide new insights into the functions of copper-dependent enzymes and contribute to a further understanding of the interplay of oxidative enzymes within fungal systems to degrade lignocellulose.

Liver transplantation and hepatocellular carcinoma: is TIPS deleterious? A multicentric retrospective study of the ARCHET research group with propensity score matching.

PURPOSE: A transjugular intrahepatic portosystemic shunt (TIPS) before the liver transplantation (LT) has been considered a contraindication in cases of hepatocellular carcinoma (HCC) because of the risk of tumour growth. We aimed to assess the impact of TIPS on incidental HCC and oncological outcomes in transplanted patients with pre-existing HCC. METHODS: All consecutive transplanted patients for cirrhosis who had a previous TIPS with or without HCC were included. Between 2007 and 2014, 1912 patients were transplanted. We included 122 (6.3%) patients having TIPS before LT. A 1:3 matched cohort of 366 patients (18.9%) having LT without previous TIPS was selected using a propensity score. Incidental HCC rate and risk factor of HCC recurrence were evaluated using multivariate analysis with a competing risk model. RESULTS: Before LT, in the TIPS group, 27 (22.1%) had an HCC vs. 81 (22.1%) in the control group (p = 1). The incidental HCC rate was similar: 10.5% (10/95) in the TIPS group vs. 6.3% (18/285) in the control group (p = 0.17). Recurrence occurred in 1/27 (3.7%) patient in the TIPS group and in 7/81 (8.6%) patients in the control group, without significant difference (p = 0.51). After multivariate regression, patient's gender (p < 0.01) was significantly associated with HCC recurrence while a tumour within Milan criteria (p = 0.01, sHR: 0.17 [0.04; 0.7]) and an incidental HCC (p<0.01) were found to be protector factors against HCC recurrence. CONCLUSION: TIPS did not worsen the prognosis of transplanted patients for HCC. TIPS should no longer be contraindicated for oncological reasons in patients with HCC waiting for an LT.

Immunohistochemical characterization of a steroid-secreting oncocytic adrenal carcinoma responsible for paraneoplastic hyperparathyroidism.

We report a unique case of a 44-year-old man with paraneoplastic hyperparathyroidism due to an oncocytic adrenocortical carcinoma (stage pT3N0R0M0, ENSAT 2 with a 4% Ki-67). Paraneoplastic hyperparathyroidism was associated with mild adrenocorticotropic hormone (ACTH)-independent hypercortisolism and increased estradiol secretion responsible for gynecomastia and hypogonadism. Biological investigations performed in blood samples from peripheral and adrenal veins revealed that the tumor secreted parathyroid hormone (PTH) and estradiol. Ectopic PTH secretion was confirmed by abnormally high expression of PTH mRNA and clusters of PTH immunoreactive cells in the tumor tissue. Double-immunochemistry studies and analysis of contiguous slides for the expression of PTH and steroidogenic markers (scavenger receptor class B type 1 [SRB1], 3ß-hydroxysteroid dehydrogenase [3ß-HSD], and aromatase) were performed. The results suggested the presence of two tumor cells subtypes with large cells with voluminous nuclei producing only PTH and that were distinct from steroid-producing cells.

Defining Benchmark Outcomes for Distal Pancreatectomy: Results of a French Multicentric Study.

OBJECTIVE: Defining robust and standardized outcome references for distal pancreatectomy (DP) by using Benchmark analysis. BACKGROUND: Outcomes after DP are recorded in medium or small-sized studies without standardized analysis. Therefore, the best results remain uncertain. METHODS: This multicenter study included all patients undergoing DP for resectable benign or malignant tumors in 21 French expert centers in pancreas surgery from 2014 to 2018. A low-risk cohort defined by no significant comorbidities was analyzed to establish 18 outcome benchmarks for DP. These values were tested in high risk, minimally invasive and benign tumor cohorts. RESULTS: A total of 1188 patients were identified and 749 low-risk patients were screened to establish Benchmark cut-offs. Therefore, Benchmark rate for mini-invasive approach was ≥36.8%. Benchmark cut-offs for postoperative mortality, major morbidity grade ≥3a and clinically significant pancreatic fistula rates were 0%, ≤27%, and ≤28%, respectively. The benchmark rate for readmission was ≤16%. For patients with pancreatic adenocarcinoma, cut-offs were ≥75%, ≥69.5%, and ≥66% for free resection margins (R0), 1-year disease-free survival and 3-year overall survival, respectively. The rate of mini-invasive approach in high-risk cohort was lower than the Benchmark cut-off (34.1% vs ≥36.8%). All Benchmark cut-offs were respected for benign tumor group. The proportion of benchmark cases was correlated to outcomes of DP. Centers with a majority of low-risk patients had worse results than those operating complex cases. CONCLUSION: This large-scale study is the first benchmark analysis of DP outcomes and provides robust and standardized data. This may allow for comparisons between surgeons, centers, studies, and surgical techniques.

A mesoporous metal-organic framework used to sustainably release copper(ii) into reducing aqueous media to promote the CuAAC click reaction.

The mesoporous metal-organic framework Cr-MIL-101-NH2 (MOF1) has been used to encapsulate, by a simple impregnation method, large amounts of copper sulfate. The resulting loaded material, Cu@MOF1, was successfully employed to slowly release copper(ii) into an appropriate reaction medium in which the reducing agent sodium ascorbate reduces copper(ii) to copper(i), thus allowing the well-known copper(i)-catalyzed alkyne-azide cycloaddition (CuAAC) "click" reaction to proceed in the absence of potentially high local copper(i) concentrations. The use of a MOF-based controlled copper release system such as Cu@MOF1 may be relevant for copper(i)-catalyzed reactions having substrates that could be degraded by potentially high local concentrations of copper(i). The copper chelating ligand TBTA (tris(benzyltriazolylmethyl)amine), a very useful ligand for click chemistry, has been successfully attached to the pores of MOF1. The resulting TBTA-functionalized MOF (MOF3) was compared with its non-functionalized version (MOF1). At copper loadings of ca. 3 mmol g-1, the results revealed that the performances of the two materials are strikingly similar. Upon immersion in methanol/water (95/5) containing sodium ascorbate, both materials slowly released copper encapsulated in their pores and could be recovered and reused efficiently for up to five reaction cycles without reloading with metal ion, while allowing the CuAAC reaction to proceed with excellent conversion rates and yields.

Representing Catalytic Mechanisms with Rule Composition.

An "imaginary transition structure" overlays the molecular graphs of the educt and product sides of an elementary chemical reaction in a single graph to highlight the changes in bond structure. We generalize this idea to reactions with complex mechanisms in a formally rigorous approach based on composing arrow-pushing steps represented as graph-transformation rules to construct an overall composite rule and a derived transition structure. This transition structure retains information about transient bond changes that are invisible at the overall level and can be constructed automatically from an existing database of detailed enzymatic mechanisms. We use the construction to (i) illuminate the distribution of catalytic action across enzymes and substrates and (ii) to search in a large database for reactions of known or unknown mechanisms that are compatible with the mechanism captured by the constructed composite rule.

Mutations Increasing Cofactor Affinity, Improve Stability and Activity of a Baeyer-Villiger Monooxygenase.

The typically low thermodynamic and kinetic stability of enzymes is a bottleneck for their application in industrial synthesis. Baeyer-Villiger monooxygenases, which oxidize ketones to lactones using aerial oxygen, among other activities, suffer particularly from these instabilities. Previous efforts in protein engineering have increased thermodynamic stability but at the price of decreased activity. Here, we solved this trade-off by introducing mutations in a cyclohexanone monooxygenase from Acinetobacter sp., guided by a combination of rational and structure-guided consensus approaches. We developed variants with improved activity (1.5- to 2.5-fold) and increased thermodynamic (+5 °C T m) and kinetic stability (8-fold). Our analysis revealed a crucial position in the cofactor binding domain, responsible for an 11-fold increase in affinity to the flavin cofactor, and explained using MD simulations. This gain in affinity was compatible with other mutations. While our study focused on a particular model enzyme, previous studies indicate that these findings are plausibly applicable to other BVMOs, and possibly to other flavin-dependent monooxygenases. These new design principles can inform the development of industrially robust, flavin-dependent biocatalysts for various oxidations.

Electric Arc Furnace Dust Recycled in 7075 Aluminum Alloy Composites Fabricated by Spark Plasma Sintering (SPS).

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.

Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis.

Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.

KRAS gene mutation quantification in the resection or venous margins of pancreatic ductal adenocarcinoma is not predictive of disease recurrence.

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.