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The safety and efficacy of minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS) remain to be established in pancreatic cancer (PDAC) Eighty-five open (O)-RAMPS were compared to 93 MI-RAMPS. The entropy balance matching approach was used to compare the two cohorts, eliminating the selection bias. Three models were created. Model 1 made O-RAMPS equal to the MI-RAMPS cohort (i.e., compared the two procedures for resectable PDAC); model 2 made MI-RAMPS equal to O-RAMPS (i.e., compared the two procedures for borderline-resectable PDAC); model 3, compared robotic and laparoscopic RAMPS. O-RAMPS and MI-RAMPS showed "non-small" differences for BMI, comorbidity, back pain, tumor size, vascular resection, anterior or posterior RAMPS, multi-visceral resection, stump management, grading, and neoadjuvant therapy. Before reweighting, O-RAMPS had fewer clinically relevant postoperative pancreatic fistulae (CR-POPF) (20.0% vs. 40.9%; p = 0.003), while MI-RAMPS had a higher mean of lymph nodes (25.7 vs. 31.7; p = 0.011). In model 1, MI-RAMPS and O-RAMPS achieved similar results. In model 2, O-RAMPS was associated with lower comprehensive complication index scores (MD = 11.2; p = 0.038), and CR-POPF rates (OR = 0.2; p = 0.001). In model 3, robotic-RAMPS had a higher probability of negative resection margins. In patients with anatomically resectable PDAC, MI-RAMPS is feasible and as safe as O-RAMPS. [ABSTRACT FROM AUTHOR]

The nearby dwarf galaxy POX 52 at z = 0.021 hosts an active galactic nucleus (AGN) with a black hole (BH) mass of M BH ∼ 105–6 M ⊙ and an Eddington ratio of ∼0.1–1. This object provides the rare opportunity to study both AGN and host-galaxy properties in a low-mass highly accreting system. To do so, we collected its multiwavelength data from X-ray to radio. First, we construct a spectral energy distribution, and by fitting it with AGN and host-galaxy components, we constrain AGN-disk and dust-torus components. Then, while considering the AGN-disk emission, we decompose optical Hubble Space Telescope images. As a result, it is found that a classical bulge component is probably present, and its mass (M bulge) is consistent with an expected value from a local relation. Lastly, we analyze new quasi-simultaneous X-ray (0.2–30 keV) data obtained by the Nuclear Spectroscopic Telescope Array and XMM-Newton. The X-ray spectrum can be reproduced by multicolor blackbody, warm and hot coronae, and disk and torus reflection components. Based on this, the spin is estimated to be a spin = 0.998−0.814, which could suggest that most of the current BH mass was achieved by prolonged mass accretion. Given the presence of the bulge, POX 52 would have undergone a galaxy merger, while the M BH– M bulge relation and the inferred prolonged accretion could suggest that AGN feedback occurred. Regarding the AGN structure, the spectral slope of the hot corona, its relative strength to the bolometric emission, and the torus structure are found to be consistent with Eddington-ratio dependencies found for nearby AGNs. [ABSTRACT FROM AUTHOR]

Most active galactic nuclei (AGNs) in the local Universe are obscured. In these obscured AGNs, an excess is usually observed in the soft X-rays below ∼2 keV above the absorbed X-ray continuum. This spectral component is associated with the scattering of X-ray photons off free electrons in the narrow-line region (NLR), and/or to photoionized lines. Recent studies have found that in highly obscured AGNs this component has lower flux relative to the primary X-ray continuum than in less obscured AGNs. This is measured by the scattering fraction, or f scatt, which is the ratio of the scattered flux to the continuum. Here, we use the ray-tracing platform reflex to perform simulations of scattered X-ray radiation to test two possible explanations for this phenomenon: (1) sources with lower f scatt are viewed at higher inclinations or (2) low f scatt sources are characterized by larger covering factors. We consider a conical NLR of free electrons, while allowing the column density and opening angle (and hence covering factor) to vary. We also consider electron densities inferred from observations, and from simulations carried out with the spectral synthesis code cloudy. Our simulations show f scatt is expected to be related to both the inclination angle and covering factor of the torus; however, the observed negative correlation between f scatt and N H can only be explained by a positive relation between the column density and the covering factor of the obscuring material. Additional contributions to f scatt can come from unresolved photoionized lines and ionized outflowing gas. [ABSTRACT FROM AUTHOR]

We investigate the X-ray variability properties of Seyfert 1 Galaxies belonging to the BAT AGN Spectroscopic Survey (BASS). The sample includes 151 unobscured (N H < 1022 cm−2) AGNs observed with XMM–Newton for a total exposure time of ∼27 ms, representing the deepest variability study done so far with high signal-to-noise XMM–Newton observations, almost doubling the number of observations analysed in previous works. We constrain the relation between the normalized excess variance and the 2–10 keV AGN luminosities, black hole masses, and Eddington ratios. We find a highly significant correlation between |$\sigma _{\rm NXS}^2$|  and M BH , with a scatter of ∼0.85 dex. For sources with high L 2–10 this correlation has a lower normalization, confirming that more luminous (higher mass) AGNs show less variability. We explored the |$\sigma _{\rm NXS}^2$|  versus M BH relation for the sub-sample of sources with M BH estimated via the 'reverberation mapping' technique, finding a tighter anticorrelation, with a scatter of ∼0.65 dex. We examine how the |$\sigma _{\rm NXS}^2$|  changes with energy by studying the relation between the variability in the hard (3–10 keV) and the soft (0.2–1 keV)/medium (1–3 keV) energy bands, finding that the spectral components dominating the hard energy band are more variable than the spectral components dominating in softer energy bands, on time-scales shorter than 10 ks. [ABSTRACT FROM AUTHOR]

Background: The presence of an aberrant right hepatic artery (a-RHA) could influence the oncological and postoperative results after pancreaticoduodenectomy (PD). Methods: A systematic review and metanalysis were conducted, including all comparative studies having patients who underwent PD without (na-RHA) or with a-RHA. The results were reported as risk ratios (RRs), mean differences (MDs), or hazard ratios (HRs) with 95% confidence intervals (95 CI). The random effects model was used to calculate the effect sizes. The endpoints were distinguished as critical and important. Critical endpoints were: R1 resection, overall survival (OS), morbidity, mortality, and biliary fistula (BL). Important endpoints were: postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), post pancreatectomy hemorrhage (PPH), length of stay (LOS), and operative time (OT). Results: Considering the R1 rate no significant differences were observed between the two groups (RR 1.06; 0.89 to 1.27). The two groups have a similar OS (HR 0.95; 0.85 to 1.06). Postoperative morbidity and mortality were similar between the two groups, with a RR of 0.97 (0.88 to 1.06) and 0.81 (0.54 to 1.20), respectively. The biliary fistula rate was similar between the two groups (RR of 1.09; 0.72 to 1.66). No differences were observed for non-critical endpoints. Conclusion: The presence of a-RHA does not affect negatively the short-term and long-term clinical outcomes of PD. [ABSTRACT FROM AUTHOR]

The benefits of immunonutrition (IM) in patients who underwent pancreatic surgery are unclear. A meta-analysis of randomized clinical trials (RCTs) comparing IM with standard nutrition (SN) in pancreatic surgery was carried out. A random-effects trial sequential meta-analysis was made, reporting Risk Ratio (RR), mean difference (MD), and required information size (RIS). If RIS was reached, false negative (type II error) and positive results (type I error) could be excluded. The endpoints were morbidity, mortality, infectious complication, postoperative pancreatic fistula (POPF) rates, and length of stay (LOS). The meta-analysis includes 6 RCTs and 477 patients. Morbidity (RR 0.77; 0.26 to 2.25), mortality (RR 0.90; 0.76 to 1.07), and POPF rates were similar. The RISs were 17,316, 7,417, and 464,006, suggesting a type II error. Infectious complications were lower in the IM group, with a RR of 0.54 (0.36–0.79; 95 CI). The LOS was shorter in IM (MD -0.3 days; −0.6 to −0.1). For both, the RISs were reached, excluding type I error. The IM can reduce infectious complications and LOS The small differences in mortality, morbidity, and POPF make it impossible to exclude type II error due to large RISs. [ABSTRACT FROM AUTHOR]

The delivery of drugs through the skin barrier at a predetermined rate is the aim of transdermal drug delivery systems (TDDSs). However, so far, TDDS has not fully attained its potential as an alternative to hypodermic injections and oral delivery. In this study, we presented a proof of concept of a dual drug-loaded patch made of nanoparticles (NPs) and ultrafine fibers fabricated by using one equipment, i.e., the electrospinning apparatus. Such NP/fiber systems can be useful to release drugs locally through the skin and the tympanic membrane. Briefly, dexamethasone (DEX)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) fiber meshes were decorated with rhodamine (RHO)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs, with RHO representing as a second drug model. By properly tuning the working parameters of electrospinning, DEX-loaded PHBHV fibers (i.e., by electrospinning mode) and RHO-loaded PLGA NPs (i.e., by electrospray mode) were successfully prepared and straightforwardly assembled to form a TDDS patch, which was characterized via Fourier transform infrared spectroscopy and dynamometry. The patch was then tested in vitro using human dermal fibroblasts (HDFs). The incorporation of DEX significantly reduced the fiber mesh stiffness. In vitro tests showed that HDFs were viable for 8 days in contact with drug-loaded samples, and significant signs of cytotoxicity were not highlighted. Finally, thanks to a beaded structure of the fibers, a controlled release of DEX from the electrospun patch was obtained over 4 weeks, which may accomplish the therapeutic objective of a local, sustained and prolonged anti-inflammatory action of a TDDS, as is requested in chronic inflammatory conditions, and other pathological conditions, such as in sudden sensorineural hearing loss treatment. [ABSTRACT FROM AUTHOR]

Three-dimensional scaffold-based culture has been increasingly gaining influence in oncology as a therapeutic strategy for tumors with a high relapse percentage. This study aims to evaluate electrospun poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) scaffolds to create a 3D model of colorectal adenocarcinoma. Specifically, the physico-mechanical and morphological properties of PCL and PLA electrospun fiber meshes collected at different drum velocities, i.e., 500 rpm, 1000 rpm and 2500 rpm, were assessed. Fiber size, mesh porosity, pore size distribution, water contact angle and tensile mechanical properties were investigated. Caco-2 cells were cultured on the produced PCL and PLA scaffolds for 7 days, demonstrating good cell viability and metabolic activity in all the scaffolds. A cross-analysis of the cell–scaffold interactions with morphological, mechanical and surface characterizations of the different electrospun fiber meshes was carried out, showing an opposite trend of cell metabolic activity in PLA and PCL scaffolds regardless of the fiber alignment, which increased in PLA and decreased in PCL. The best samples for Caco-2 cell culture were PCL500 (randomly oriented fibers) and PLA2500 (aligned fibers). Caco-2 cells had the highest metabolic activity in these scaffolds, with Young's moduli in the range of 8.6–21.9 MPa. PCL500 showed Young's modulus and strain at break close to those of the large intestine. Advancements in 3D in vitro models of colorectal adenocarcinoma could move forward the development of therapies for this cancer. [ABSTRACT FROM AUTHOR]

The analysis of complex systems tends to be approached through a separation and a simplification of the main macro phenomena and, thus, addressed through dedicated techniques, tools, and algorithms. A smart and interesting possibility, instead, is represented by the so-called model-based design analysis, which allows one to interface phenomena coming from interactions of different physical natures. This paper aims to propose a multi-physics Matlab/Simulink®-based architecture that allows one to integrate general and strongly non-linear coupling phenomena, taking efforts from two novel implemented bi-directional co-simulation routines based on Spice® and ESRF Radia® engines. Emphasis is dedicated to the discussion and description of the co-simulation algorithms and processes characteristic of these routines, which allow the analog electronic and the magneto dynamic domain's integration under a single simulation environment. To highlight the reliability of the multi-domain architecture and to validate the reported co-simulation results, a comparison with the experimental measures obtained on an innovative MEMS electromagnetic actuator are proposed. [ABSTRACT FROM AUTHOR]

We present the first systematic broad-band X-ray study of super-Eddington accretion onto supermassive black holes with simultaneous NuSTAR and XMM–Newton or Swift /XRT observations of a sample of eight super-Eddington accreting Active Galactic Nuclei (AGNs) with Eddington ratio 1 < λ Edd < 426. We find that the super-Eddington accreting massive black holes (SEAMBHs) show a steep primary continuum slope as expected for sources accreting in the super-Eddington regime, mostly dominated by relativistic reflection. The iron K α emission lines of the sources of our sample show relativistic broadening. In addition, the equivalent widths of the narrow components of the iron K α lines follow the 'X-ray Baldwin' effect, also known as the 'Iwasawa–Taniguchi' effect. We found a statistically significant correlation between the photon index of the primary power law and the Eddington ratio, consistent with past studies. Moreover, as expected for super-Eddington sources, the median value of the reflection fraction of the sources we analysed is a factor ∼ 2 higher than the median reflection fraction value of the type 1 AGN from the BASS sample. We are able to estimate the coronal temperature for three sources of our sample: Mrk 382 (kT e = 7.75 keV), PG 0026+129 (kT e = 39 keV), and IRAS 04416+1215 (kT e = 2.95 keV). Looking at the position of the SEAMBHs sources of our sample in the compactness–temperature diagram it appears that in super-Eddington AGN, as for lower Eddington ratio AGN, the X-ray corona is controlled by pair production and annihilation. [ABSTRACT FROM AUTHOR]

Background: The advantages of LPD compared with OPD remain debatable. The study aimed to compare the laparoscopic (LPD) versus open (OPD) for pancreaticoduodenectomy. Methods: A meta-analysis of randomized studies (RCTs) comparing LPD and OPD was made. The results were reported as relative risk (RRs) or mean differences (MDs). The trial sequential analysis was used to test the type I and type II errors defining the required information size (RIS). The primary outcome was mortality, major morbidity, and postoperative pancreatic fistula (POPF). R1 resection, post-pancreatectomy hemorrhage, delayed gastric emptying, biliary fistula, reoperation, readmission, operative time (OT), lymph nodes harvested, and length of stay (LOS) were also studied. Results: Four RCTs, counting 818 patients, were found. The RRs for mortality, major morbidity, and POPF were 1.16, 1.04, and 0.86, without significant differences. The RISs were 35,672, 16,548, and 8206. To confirm this equivalence, at least 34,854, 15,730, and 7338 should be randomized. OT was significantly longer in LPD than OPD, with an MD of 63.22. The LOS was significantly shorter in LPD than in OPD, with − 1.76 days. The RISs were 1297 and 1273, excluding a false-positive result. No significant differences were observed for the remaining endpoints, and RISs suggested that more than 3000 patients should be randomized to confirm the equivalence. Conclusion: The equivalence of LPD and OPD for mortality, major morbidity, and POPF is affected by type II error. The RISs to demonstrate a superiority of one of the two techniques seem unrealistic to obtain. [ABSTRACT FROM AUTHOR]

Purpose: The aim is to clarify the use of perioperative chemotherapy in resectable goblet cell carcinoma (GCC). Methods: A retrospective study was carried out based on the Surveillance, Epidemiology, and End Results study. The population was divided: into patients who received only radical surgery (group A) and those who received radical surgery plus chemotherapy (group B). An entropy balancing was carried out to correct the imbalance between the two groups. Two models were generated. Model 1 contained only high-risk patients: group B and a “virtual” group A with similar characteristics. Model 2 included only low-risk patients: group A and “virtual” group B with identical attributes. The efficacy of entropy balancing was evaluated with the d value. The overall survival was compared and reported with Hazard Ratio (HR) within a confidence interval of 95% (95 CI). Results: The groups A and B were imbalanced for tumor size (d = 0.392), T (d = 1.128), N (d = 1.340), M (d = 1.456), mean number of positive lymph nodes (d = 0.907), and LNR (d = 0.889). Before the balancing, the risk of death was higher in group B than in A (4.3; 2.5 to 7.4). After reweighting, all large differences were eliminated (d < 0.200). In high-risk patients, the risk of death was higher in patients who underwent surgery alone than those who received perioperative chemotherapy (HR 0.5; 0.2 to 1.3) without statistical significance (p = 0.187). In low-risk patients, the risk of death was similar (HR 1.1; 0.3 to 3.3). Conclusion: Perioperative chemotherapy could provide some marginal advantages to high-risk patients. [ABSTRACT FROM AUTHOR]

Changing-look (CL) AGN are unique probes of accretion onto supermassive black holes (SMBHs), especially when simultaneous observations in complementary wavebands allow investigations into the properties of their accretion flows. We present the results of a search for CL behaviour in 412 Swift -BAT detected AGN with multiple epochs of optical spectroscopy from the BAT AGN Spectroscopic Survey (BASS). 125 of these AGN also have 14–195  keV ultra-hard X-ray light curves from Swift -BAT which are contemporaneous with the epochs of optical spectroscopy. Eight CL events are presented for the first time, where the appearance or disappearance of broad Balmer line emission leads to a change in the observed Seyfert type classification. Combining with known events from the literature, 21 AGN from BASS are now known to display CL behaviour. Nine CL events have 14–195  keV data available, and five of these CL events can be associated with significant changes in their 14–195  keV flux from BAT. The ultra-hard X-ray flux is less affected by obscuration and so these changes in the 14–195 keV band suggest that the majority of our CL events are not due to changes in line-of-sight obscuration. We derive a CL rate of 0.7–6.2 per cent on 10–25 yr time-scales, and show that many transitions happen within at most a few years. Our results motivate further multiwavelength observations with higher cadence to better understand the variability physics of accretion onto SMBHs. [ABSTRACT FROM AUTHOR]

Background: The antiproliferative activity of a high dose of somatostatin analogs (HD-SSA) in treating gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) remains under debate. Methods: A systematic review and proportion meta-analysis were made. The primary endpoint was the efficacy measured as incidence density ratio (IDR) at one year. The secondary endpoints were the disease control rate (DCR) and severe adverse events (SAEs). The heterogeneity (I2), when high (>50%), was interpreted by performing a univariate metaregression analysis, analyzing as covariates: type and design of the study, location (Europe or USA), sample size, grading according to 2017 WHO, the metastatic disease rate, previous therapy including surgery, and quality of the study. Results: A total of 11 studies with 783 patients were included. The IDR was 62 new progressions of 100 patients treated with HD-SSA every one year. The heterogeneity was high. The study's year, type and design, primary tumor, grading, previous treatments, and quality of the studies did not influence the IDR. The IDR was significantly higher in USA centers and studies with more than 50 patients. The IDR was lower when a high rate of metastatic patients was present in the studies. The DCR was 45%. The heterogeneity was high. The DCR was lower in USA studies and in prospective trials. Conclusion: Given the limited efficacy of HD-SSA in preventing the disease progression in unresectable GEP-NENs after failure of standard dose SSA, the use of this therapeutic approach is advisable in selected cases when other antiproliferative treatments are not feasible. [ABSTRACT FROM AUTHOR]

We present a detailed study of the highly obscured active galaxy NGC 4507, performed using four Nuclear Spectroscopic Telescope Array (NuSTAR) observations carried out between May and August in 2015 (∼130 ks in total). Using various phenomenological and physically motivated torus models, we explore the properties of the X-ray source and those of the obscuring material. The primary X-ray emission is found to be non-variable, indicating a stable accretion during the period of the observations. We find the equatorial column density of the obscuring materials to be ∼2 × 1024 cm−2 while the line-of-sight column density to be ∼7–8 × 1023 cm−2. The source is found to be deeply buried with the torus covering factor of ∼0.85. We observe variability in the line-of-sight column density on a time-scale of <35 d. The covering factor of the Compton-Thick material is found to be ∼0.35 in agreement with the results of recent X-ray surveys. From the variability of the line-of-sight column density, we estimate that the variable absorbing material is likely located either in the BLR or in the torus. [ABSTRACT FROM AUTHOR]

Reprocessed X-ray emission in active galactic nuclei can provide fundamental information about the circumnuclear environments of supermassive black holes. Recent mid-infrared studies have shown evidence of an extended dusty structure perpendicular to the torus plane. In this work, we build a self-consistent X-ray model for the Circinus Galaxy including the different physical components observed at different wavelengths and needed to reproduce both the morphological and spectral properties of this object in the mid-infrared. The model consists of four components: the accretion disc, the broad-line region (BLR), a flared disc in the equatorial plane, and a hollow cone in the polar direction. Our final model reproduces well the 3–70 keV Chandra and NuSTAR spectra of Circinus, including the complex Fe Kα zone and the spectral curvature, although several additional Gaussian lines, associated with either ionized iron or broadened Fe Kα/Kβ lines, are needed. We find that the flared disc is Compton-thick (⁠|$N_{\rm H,d}= \rm 1.01^{+0.03}_{-0.24}\times 10^{25}\, cm^{-2}$|⁠) and geometrically thick (⁠|$\mathrm{ CF}=0.55^{+0.01}_{-0.05}$|⁠), and that the hollow cone has a Compton-thin column density (⁠|$N_{\rm H,c}= \rm 2.18^{+0.47}_{-0.43}\times 10^{23}\, cm^{-2}$|⁠), which is consistent with the values inferred by mid-infrared studies. Including also the BLR, the effective line-of-sight column density is |$N_{\rm H}= \rm 1.47^{+0.03}_{-0.24}\times 10^{25}\, cm^{-2}$|⁠. This approach to X-ray modelling, i.e. including all the different reprocessing structures, will be very important to fully exploit data from future X-ray missions. [ABSTRACT FROM AUTHOR]

Simple Summary: Development of new therapeutics to treat osteosarcoma is fundamental to decreasing its current health impact. 3D in vitro models are gaining tremendous momentum as, compared to traditional 2D in vitro models and in vivo models, can speed up new treatment discovery and provide clarification of the pathology development, by ultimately offering a reproducible and biomimetic tool. However, engineering a 3D osteosarcoma in vitro model is challenging, since the reliability of the models strictly depends on their ability to correctly mimic the physical, mechanical, and biological properties of the pathological tissue to be replicated. Here, we designed 3D printed polyurethane scaffolds enriched by in vitro pre-generated bone extracellular matrix, synthesized by osteo-differentiated human mesenchymal stromal cells, to replicate in vitro an osteosarcoma model, which can be potentially used to study tumor progression and to assess new treatments. Osteosarcoma is a primary bone tumor characterized by a dismal prognosis, especially in the case of recurrent disease or metastases. Therefore, tools to understand in-depth osteosarcoma progression and ultimately develop new therapeutics are urgently required. 3D in vitro models can provide an optimal option, as they are highly reproducible, yet sufficiently complex, thus reliable alternatives to 2D in vitro and in vivo models. Here, we describe 3D in vitro osteosarcoma models prepared by printing polyurethane (PU) by fused deposition modeling, further enriched with human mesenchymal stromal cell (hMSC)-secreted biomolecules. We printed scaffolds with different morphologies by changing their design (i.e., the distance between printed filaments and printed patterns) to obtain different pore geometry, size, and distribution. The printed PU scaffolds were stable during in vitro cultures, showed adequate porosity (55–67%) and tunable mechanical properties (Young's modulus ranging in 0.5–4.0 MPa), and resulted in cytocompatible. We developed the in vitro model by seeding SAOS-2 cells on the optimal PU scaffold (i.e., 0.7 mm inter-filament distance, 60° pattern), by testing different pre-conditioning factors: none, undifferentiated hMSC-secreted, and osteo-differentiated hMSC-secreted extracellular matrix (ECM), which were obtained by cell lysis before SAOS-2 seeding. Scaffolds pre-cultured with osteo-differentiated hMSCs, subsequently lysed, and seeded with SAOS-2 cells showed optimal colonization, thus disclosing a suitable biomimetic microenvironment for osteosarcoma cells, which can be useful both in tumor biology study and, possibly, treatment. [ABSTRACT FROM AUTHOR]

Background: The superiority of Blumgart anastomosis (BA) over non-BA duct to mucosa (non-BA DtoM) still remains under debate. Methods: We performed a systematic search of studies comparing BA to non-BA DtoM. The primary endpoint was CR-POPF. Postoperative morbidity and mortality, post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), reoperation rate, and length of stay (LOS) were evaluated as secondary endpoints. The meta-analysis was carried out using random effect. The results were reported as odds ratio (OR), risk difference (RD), weighted mean difference (WMD), and number needed to treat (NNT). Results: Twelve papers involving 2368 patients: 1075 BA and 1193 non-BA DtoM were included. Regarding the primary endpoint, BA was superior to non-BA DtoM (RD = 0.10; 95% CI: −0.16 to −0.04; NNT = 9). The multivariate ORs' meta-analysis confirmed BA's protective role (OR 0.26; 95% CI: 0.09 to 0.79). BA was superior to DtoM regarding overall morbidity (RD = −0.10; 95% CI: −0.18 to −0.02; NNT = 25), PPH (RD = −0.03; 95% CI −0.06 to −0.01; NNT = 33), and LOS (− 4.2 days; −7.1 to −1.2 95% CI). Conclusion: BA seems to be superior to non-BA DtoM in avoiding CR-POPF. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic adrenalectomy has a well-demonstrated learning curve in the first generation of laparoscopic surgeons. Data about the second generation of laparoscopic surgeons are lacking.Methods: In this retrospective observational study, data from patients undergoing laparoscopic adrenalectomy from 2000 to 2019 in a high-volume center were collected and analyzed. The cumulative sum of procedures of each surgeon and the operating time were evaluated. A multivariate analysis with backward stepwise logistic regression was carried out to define which factors influenced the operative time. Three surgeons performed the analyzed procedures: a senior surgeon who began his laparoscopic activity without receiving specific training or supervision and two young surgeons, who performed their procedures under the guidance of the "senior" experienced surgeon. The first 38 procedures of the three surgeons were then compared.Results: A total of 244 laparoscopic adrenalectomies were performed. Age, clinical diagnosis, side of the lesion, body mass index, comorbidities, Charlson index, American Society of Anaesthesiologists (ASA) score, and lower abdominal surgery were found to have no significant relationship with the operative time (p > 0.05). Gender, symptoms, previous upper abdominal surgery, size of the lesion, and cumulative sum of procedures were independent predictors of operative time. In the comparison between different surgeons, operative time resulted significantly longer for the senior (165 min; 140-180) than for the two junior surgeons (137.5 min; 115-160; p = 0.003 and 130 min; 120-170; p = 0.001).Conclusions: The presence of a mentor in operative theater and specific training programs could be useful during the learning period. The cumulative sum of procedures related to the operative time represents a good parameter to measure the acquired expertise of a surgeon. [ABSTRACT FROM AUTHOR]

The Clavien-Dindo classification (CDC) system and Comprehensive Complication Index (CCI®) are both widely used methods for reporting the burden of postoperative complications. This study aimed to compare the accuracy of the CDC and CCI® in predicting outcomes associated with pancreatic surgery. The CCI® and CDC were applied to 668 patients who underwent pancreatic resection. Length of postoperative stay (LOS) was chosen as the primary outcome variable. The comparison between CCI® and CDC was made with the Spearman test, reporting þs with standard error (SE) and logistic regression, reporting the Odds Ratio (OR) and Area Under the Curve with SE. The median value with the interquartile range (IQR) of CCI® was 20.9 (0–29.6). Both CCI® (þs = 0.609) and CDC (0.590) were significantly (P < 0.001) correlated to LOS. CCI (OR 1.056 and OR 1.052) and CDC (OR 1.978, and OR 1.994) predicted (P < 0.001) LOS over the median and 75th percentile. The accuracy of CCI® was superior to CDC for LOS over 50th (0.785 vs. 0.740; P = 0.004) and over 75th (0.835 vs. 0.761; P < 0.001) percentile. The accuracy of CCI® in measuring the complicated postoperative course was superior to CDC, correctly classifying eight patients every ten tested. [ABSTRACT FROM AUTHOR]

Background: The Blumgart anastomosis is a method of pancreaticojejunostomy after pancreaticoduodenectomy (PD) which combines the principle of duct-to-mucosa anastomosis with an invagination technique of the pancreas. Methods: Retrospective study involving consecutive patients who underwent pancreaticoduodenectomy for pancreatic head cancer. Data predictive of pancreatic fistula and postoperative outcomes were collected. The patients were divided into three groups and were compared based on the type of pancreatic anastomosis performed: Blumgart anastomosis (BA), duct-to-mucosa anastomosis (DtoM), and invagination pancreaticojejunostomy (PJ). The primary endpoint was to determine the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF). The secondary endpoints were to determine whether postoperative pancreatic fistula grade C (POPF C) and/or severe complications occurred as well as to determine the reoperation rate and 30- and 90-day mortality. A propensity score matching analysis was used. Results: Using propensity score matching (PSM), the occurrence of CR-POPF was not significantly different between the BA (21.6%) and the other pancreatic anastomoses (all 31.1%, DtoM = 27.0%; PJ = 35.1%). However, the BA significantly reduced (1) severe complications (0 versus 35.1%; P < 0.001) and 90-day mortality (0% versus 12.2%; P = 0.028) with respect to all anastomoses; (2) severe complications (0% versus 29.7%; P < 0.001), POPF grade C (0% versus 16.2%; P = 0.025), and reoperation (2.7% versus 16.2%; P = 0.056) with respect to DtoM; and (3) severe complications (0% versus 40.5%; P < 0.001) and 90-day mortality (0% versus 13.5%; P = 0.054) with respect to PJ. Conclusions: Applying the PSM analysis for the first time, the present study seemed to suggest that the BA succeeded in minimizing severe complications after PD. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic distal pancreatectomy (LDP) represents a challenging procedure with a high conversion rate. A nomogram is a simple statistical predictive tool which is superior to risk groups. The aim of this study was to develop and validate a preoperative nomogram for predicting the probability of conversion from laparoscopic to open distal pancreatectomy. Methods: This is a retrospective study of 100 consecutive patients who underwent LDP. For each patient demographic, pre-intra- and postoperative data were collected. Univariate and multivariate analyses were carried out to identify the factors significantly influencing the conversion rate. The effect of each factor was weighted using the beta coefficient (β), and a nomogram was built. Finally, a logistic regression between the score and the conversion rate was carried out to calibrate the nomogram. Results: The conversion rate was 19.0%. At multivariate analysis, female (β = − 1.8 ± 0.9; P = 0.047) and tail location of the tumor (β = − 2.1 ± 1.1; P = 0.050) were significantly related to a low probability of conversion. Body mass index (BMI) (β = 0.2 ± 0.1; P = 0.011) and subtotal pancreatectomy (β = 2.4 ± 0.9; P = 0.006) were factors independently related to a high probability of conversion. The nomogram constructed had a minimum value of 4 and a maximum value of 18 points. The probability of conversion increased significantly starting from a minimum score of 6 points (P = 0.029; conversion probability 14.4%; 95%CI, 1.5–27.3%) up to 16 (P = 0.048; 27.8%; 95%CI, 0.2–48.7%). Conclusion: The nomogram proposed could serve as an effective preoperative tool capable of assessing the probability of conversion, allowing to take reliable decisions regarding indications and adequate stepwise training program of LDP. [ABSTRACT FROM AUTHOR]

Laparoscopic distal pancreatectomy (LDP) is a challenging operation due to technical complexity and tumor-related factors. Aim of this study was to identify preoperative risk factors affecting LDP difficulty. Consecutive patients who underwent LDP between 2015 and 2018 at San Raffaele Hospital and Policlinico S.Orsola-Malpighi Hospital were enrolled retrospectively. Three variables were used to define surgical difficulty: conversion to open, duration of surgery >3rd quartile and intraoperative blood loss >3rd quartile. The presence of ≥1 of these 3 variables was considered as another measure of difficulty. Overall, 191 patients were included. Conversion to open was required in 25 patients (13%). At multiple regression analysis, tumor proximity to major vessels was the only independent predictor of conversion from laparoscopic to open (p < 0.001). No variables independently predicted an excessive duration of surgery. Male gender (p = 0.033) and increasing parenchymal thickness at resection line (p = 0.018) were independent predictors of excessive blood loss. Increasing parenchymal thickness at resection line (p = 0.014) and tumor proximity to major vessels (p = 0.002) were significant risk factors for the presence of ≥1 outcome of surgical difficulty. Male gender, increasing parenchymal thickness at resection line and tumor proximity to major vessels represent preoperative risk factors of LDP difficulty. [ABSTRACT FROM AUTHOR]

Overall survival (OS) is considered as the standard measure of outcome in oncology. However, considering that resectable pancreatic neuroendocrine neoplasms (Pan-NENs) usually have a long OS, the feasibility of prospective studies is questionable due to a long follow-up period needed. The primary endpoint was to validate the use of disease-free survival (DFS) as a surrogate measure of OS. The secondary endp oint was to calculate the gain in sample size using DFS instead of OS in hypothetical pro spective studies with two parallel groups. A systematic review of studies reporting both OS and DFS in resected Pan-NENs was carried out. Multivariate linear regression analysis was used to evaluate if DFS predicts the OS in patients undergoing radical resection. Monte Carlo simulation was performed to estimate the gain in sample size, supposing the use of DFS instead of OS, to evaluate a hypothetical adjuvant treatment after surgery in a randomized trial. Six studies reporting data about seven cohorts of resected Pan-NENs were included, for a total of 1088 patients. The median OS and DFS were 144 (27-13 4) and 122 (50-267) months, respectively. There was a significant correlation between DFS and OS (R2 = 0.988; P = 0.035). Monte Carlo simulations showed that the number of patients needed to demonstrate a significant reduction of probability of a 'target event' in a hypothetical twoarm group exploring the hypothetical role of adjuvant therapy was reduced using DFS instead OS. This finding supports the legitimacy of using DFS as an acceptable surrogate for OS in surgical clinical trials. [ABSTRACT FROM AUTHOR]

The multiorgan procurement (MOP) represents a chance for the general surgery resident to learn the fundamental steps of open abdominal surgery. The objective of this study was to evaluate the impact of MOP on the residents' open surgical skills. Residents' surgical skills were assessed during a 6-month transplant rotation (October 2020-March 2021) using a modified Objective Structured Assessment of Technical Skills with the global rating scale. The surgeries were self-assessed by residents and tutors based on 9 specific steps (SS) and 4 general skills (GS). Each item was rated from 1 (poor) to 5 (excellent) with a maximum score of 45 points for SS and 20 for GS. A crossed-effects linear regression analysis was performed both to evaluate any associations between GS/SS scores and some prespecified covariates , and to study differences in the assessments performed by residents and tutors. Residents actively participated in a total of 59 procurements. In general, there were no significant differences in SS/GS mean scorings between residents (n = 15) and tutors (n = 5). There was a significantly positive association between mean GS/SS scorings and the number of donor surgeries performed (at least 5). Comparing the evaluations of the tutors with the residents, this significance was retained only when scorings were assigned by the tutors. MOP was shown to improve basic open surgical skills among residents. Awareness of the utility of a clinical rotation in transplant surgery should be raised also on an institutional level. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic distal pancreatectomy represents a difficult surgical procedure with an high conversion rate to open procedure. The factors related to its difficulty and conversion to open distal pancreatectomy were rarely reported. The aim of the present study was to identify which factors are related to conversion from laparoscopic to open distal pancreatectomy.Methods: A retrospective study of a prospective database of 68 patients who underwent laparoscopic distal pancreatectomy was conducted at a high-volume center by pancreatic surgeons experienced with laparoscopic surgery. Pre-intra and postoperative data were collected. Patients who completed a laparoscopic distal pancreatectomy were compared with those who needed a conversion to the open approach as regard demographic, clinical, radiological, and surgical data. Univariate and multivariate analyses were carried out.Results: Univariate analysis suggested that the site of the lesion, the extension of pancreatic resection, and the requirement for an extended procedure to adjacent organs were significantly associated with the risk of conversion to the open approach. Multivariate analysis showed that only the extension of the pancreatic resection (subtotal pancreatectomy) was significantly related to the odds of conversion [odds ratio (OR) 19.5; 95% confidence interval (CI) 1.1-32.3; P = 0.038]. Preoperative suspicion of malignancy differed between the two groups; however, this difference did not reach statistical significance (P = 0.078).Conclusions: Despite the limitations of the study, only the extension of pancreatic resection seemed to be the main factor related to conversion during laparoscopic distal pancreatectomy. [ABSTRACT FROM AUTHOR]

Background: Many mini-invasive pancreaticoduodenectomy (MIPD) techniques have been reported, but their advantages with respect to an open technique (OPD) and with respect to each other are unclear.Method: A systematic literature search of studies comparing different types of MIPD was carried out: laparoscopic-assisted (LAPD), totally robotic (TRPD), totally laparoscopic (TLPD) or totally laparoscopic—robotic assisted (TLPD-RA) to OPD. The primary endpoint was postoperative mortality. The secondary endpoints were intraoperative, postoperative and oncological outcomes. A network meta-analysis was designed to generate direct, indirect and mixed estimate effects, between different approaches, for each variable. The effects were reported as pairwise comparisons and hierarchical ranking as to each approach could be the best or the worst for each outcome, expressed by the surface under the cumulative ranking curve.Results: Twenty studies were identified, involving 2759 patients: 1813 OPDs, 81 LAPDs, 505 TRPDs, 224 TLPDs and 136 TLPD-RAs. No differences regarding postoperative mortality were found in pairwise comparison. The LAPD technique had a high probability of being the worst approach, while TRPD had a high probability of being one of the best. Regarding the secondary endpoints, OPD was the best regarding operative time and postoperative bleeding, but the worst regarding blood loss and wound infection. The TRPD or TLPD-RA techniques seemed to be the best for delayed gastric emptying, length of hospital stay, harvested lymph nodes and postoperative morbidity. The TLPD technique was often the worst approach, especially for overall and major complications, postoperative bleeding and biliary leak.Conclusion: The safest MIPDs are those involving a robotic system which seems to have a promising role in ameliorating the outcomes of OPD, especially when compared to a laparoscopic approach. [ABSTRACT FROM AUTHOR]

We study the relation between accretion rate (in terms of L/LEdd) and shape of the hard X-ray spectral energy distribution (namely the photon index Γx) for a large sample of 228 hard X-ray-selected, low-redshift active galactic nuclei (AGNs), drawn from the Swift/BAT AGN Spectroscopic Survey (BASS). This includes 30 AGNs for which black hole mass (and therefore L/LEdd) is measured directly through masers, spatially resolved gas or stellar dynamics, or reverberation mapping. The high-quality and broad energy coverage of the data provided through BASS allow us to examine several alternative determinations of both Γx and L/LEdd. For the BASS sample as a whole, we find a statistically significant, albeit very weak correlation between Γx and L/LEdd. The best-fitting relations we find, Γx ≅ 0.15 log L/LEdd + const., are considerably shallower than those reported in previous studies. Moreover, we find no corresponding correlations among the subsets of AGN with different MBH determination methodology. In particular, we find no robust evidence for a correlation when considering only those AGN with direct or single-epoch MBH estimates. This latter finding is in contrast to several previous studies which focused on z > 0.5 broad-line AGN. We discuss this tension and conclude that it can be partially accounted for if one adopts a simplified, power-law X-ray spectral model, combined with L/LEdd estimates that are based on the continuum emission and on single-epoch broad-line spectroscopy in the optical regime. We finally highlight the limitations on using Γx as a probe of supermassive black hole evolution in deep extragalactic X-ray surveys. [ABSTRACT FROM AUTHOR]

Purpose: Two main techniques are commonly used during laparoscopic right hemicolectomy in order to perform the ileocolic anastomosis: intracorporeal (IA) and extracorporeal (EA). The aim of this study was to evaluate the safety of the two techniques. Methods: A systematic review was carried out to identify studies comparing IA and EA. The primary endpoint was anastomotic leakage. The secondary endpoints were intra- and postoperative results. A meta-analysis was carried out using the random-effects model. Results: Fourteen studies matched the selection criteria, enrolling 1717 patients (50.3 % IA, 49.7 % EA). The anastomotic leakage was similar in the IA and the EA groups (3.4 vs. 4.6 %, respectively) with a risk difference (RD) of −0.01 (95 % CI = −0.03 to 0.01; P = 0.120). IA group had lower overall complication rate (27.6 vs. 38.4 %; RD = −0.15; 95 % CI = 0.27 to −0.04; P = 0.009) and wound infection rate (4.9 vs. 8.9 %; RD = 0.52; −0.03; 95 % CI = −0.06 to −0.01; P = 0.030). Time to first oral intake (weighted mean difference (WMD) = −1; 95 % CI = −1.59 to −0.41; P < 0.001), length of hospital stay (WMD = −1.13; 95 % CI = −1.90 to −0.35; P = 0.004) and minilaparotomy size (WMD = −26; 95 % CI = −38 to −13; P < 0.001) were shorter in IA patients. The incisional hernia rate was lower in the IA group (2.3 vs. 13.7 %) with an RD of −0.09 (95 % CI = −0.17 to −0.02; P = 0.020). There were no differences in operative time, blood loss, conversion, internal hernia, reoperation, mortality, time to first flatus and defecation, analgesic required, number of lymph nodes harvested and length of distal margin. Conclusions: Laparoscopic right hemicolectomy with IA is a safe alternative to EA. Additional well-structured, prospective randomised trials are needed to confirm all the advantages regarding postoperative results which were pointed out in our study. [ABSTRACT FROM AUTHOR]

Background: Total pancreatectomy is actually considered a viable option in selected patients even if large comparative studies between partial versus total pancreatectomy are not currently available. Our aim was to evaluate whether total pancreatectomy can be considered as feasible, safe, efficacious, and cost-effective as pancreaticoduodenectomy.Methods: A single center, prospective, observational trial, regarding postoperative outcomes, long-term results, and cost-effectiveness, in a tertiary referral center was conducted, comparing consecutive patients who underwent elective total pancreatectomy and/or pancreaticoduodenectomy.Results: Seventy-three consecutive elective total pancreatectomies and 184 pancreaticoduodenectomies were compared. There were no significant differences regarding postoperative outcomes and overall survival. The quality of life, evaluated in 119 patients according to the EQ-5D-5L questionnaire, showed that there were no significant differences regarding the five items considered. The mean EQ-5D-5L score was similar in the two procedures (total pancreatectomy = 0.872, range 0.345-1.000; pancreaticoduodenectomy = 0.832, range 0.393-1.000; P = 0.320). The impact of diabetes according to the Problem Areas in Diabetes (PAID) questionnaire did not show any significant differences except for question 13 (total pancreatectomy = 0.60; pancreaticoduodenectomy = 0.19; P = 0.022). The cost-effectiveness analysis suggested that the quality-adjusted life year was not significantly different between the two procedures (total pancreatectomy = 0.910, range 0.345-1.000; pancreaticoduodenectomy = 0.910, range -0.393-1.000; P = 0.320).Conclusions: From this study, it seems reasonable to suggest that total pancreatectomy can be considered as safe, feasible, and efficacious as PD and acceptable in terms of cost-effectiveness. [ABSTRACT FROM AUTHOR]

The primary source of emission of active galactic nuclei (AGNs), the accretion disc, is surrounded by an optically and geometrically thick dusty structure ('the so-called dusty torus'). The infrared radiation emitted by the dust is nothing but a reprocessed fraction of the accretion disc emission, so the ratio of the torus to the AGN luminosity (Ltorus/LAGN) should corresponds to the fraction of the sky obscured by dust, i.e. the covering factor. We undertook a critical investigation of the Ltorus/LAGN as the dust covering factor proxy. Using state-of-the-art 3D Monte Carlo radiative transfer code, we calculated a grid of spectral energy distributions (SEDs) emitted by the clumpy two-phase dusty structure. With this grid of SEDs, we studied the relation between Ltorus/LAGN and the dust covering factor for different parameters of the torus. We found that in the case of type 1 AGNs the torus anisotropy makes Ltorus/LAGN underestimate low covering factors and overestimate high covering factors. In type 2 AGNs Ltorus/LAGN always underestimates covering factors. Our results provide a novel easy-to-use method to account for anisotropy and obtain correct covering factors. Using two samples from the literature, we demonstrated the importance of our result for inferring the obscured AGN fraction. We found that after the anisotropy is properly accounted for, the dust covering factors show very weak dependence on LAGN, with values in the range of ≈0.6-0.7. Our results also suggest a higher fraction of obscured AGNs at high luminosities than those found by X-ray surveys, in part owing to the presence of a Compton-thick AGN population predicted by population synthesis models. [ABSTRACT FROM AUTHOR]

Background: Data regarding the quality of life in patients undergoing laparoscopic distal pancreatectomy are lacking and no studies have reported a real cost-effectiveness analysis of this surgical procedure. The aim of this study was to evaluate and compare the quality of life and the cost-effectiveness of a laparoscopic distal pancreatectomy with respect to an open distal pancreatectomy. Methods: Forty-one patients who underwent a laparoscopic distal pancreatectomy and 40 patients who underwent an open distal pancreatectomy were retrospectively studied as regards postoperative results, quality of life and cost-effectiveness analysis. The Italian neutral version of the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C-30, version 3.0, was used to rate the quality of life. Results: Postoperative results were similar in the two groups; the only difference was that the first oral intake took place significantly earlier in the laparoscopic group than in the open group ( P < 0.001). Regarding quality of life, the laparoscopic approach was able to ameliorate physical functioning ( P = 0.049), role functioning ( P = 0.044) and cognitive functioning ( P = 0.030) and reduce the sleep disturbance scale ( P = 0.050). The cost-effectiveness analysis showed that the acceptability curve for a laparoscopic distal pancreatectomy had a higher probability of being more cost-effective than an open distal pancreatectomy when a willingness to pay above 5400 Euros/quality-adjusted life years (QALY) was accepted. Conclusion: Despite the limitations of the study, laparoscopic distal pancreatectomy can be considered not only safe and feasible but also permits a better quality of life and is acceptable in terms of cost-effectiveness to Italian and European health care services. [ABSTRACT FROM AUTHOR]

The circumnuclear material around active galactic nuclei (AGNs) is one of the essential components of the obscuration-based unification model. However, our understanding of the circumnuclear material in terms of its geometrical shape, structure, and its dependence on accretion rate is still debated. In this paper, we present the multi-epoch broad-band X-ray spectral modelling of a nearby Compton-thick AGN in Circinus galaxy. We utilize all the available hard X-ray (>10 keV) observations taken from different telescopes, i.e. BeppoSAX, Suzaku, NuSTAR , and AstroSat , at 10 different epochs across 22 yr from 1998 to 2020. The 3.0–79 keV broad-band X-ray spectral modelling using physically motivated models, namely MYTorus, borus02 , and uxclumpy , infers the presence of a torus with a low covering factor of 0.28, an inclination angle of 77°–81° and Compton-thick line-of-sight column densities (N H,LOS = 4.13–9.26 × 1024 cm−2) in all the epochs. The joint multi-epoch spectral modelling suggests that the overall structure of the torus is likely to remain unchanged. However, we find tentative evidence for the variable line-of-sight column density on time-scales ranging from 1 d to 1 week to a few years, suggesting a clumpy circumnuclear material located at subparsec to tens of parsec scales. [ABSTRACT FROM AUTHOR]

Purpose: Soft pancreatic parenchyma is the most widely recognized risk factor for pancreatic fistula. We conducted this study to clarify if there are preoperative factors related to a soft pancreatic remnant and to establish if they are useful for predicting pancreatic fistula. Methods: This was a retrospective study of patients who underwent pancreatic resections at the Department of Surgical Sciences of the S. Orsola-Malpighi Hospital, Bologna, Italy. The factors considered were sex, age, co-morbidities, body mass index, American Society of Anesthesiologists score, characteristics of the pancreatic remnant, and preoperative diagnosis. Results: Data from 208 patients were recorded. The risk factors predictive of a soft pancreatic remnant were BMI >24 kg/m ( P = 0.011), a Wirsung duct size ≤3 mm ( P < 0.001), and coexisting periampullary diseases ( P < 0.001). Using these factors, we developed a risk score model that was validated by considering the pancreatic fistula rate. The overall and clinically relevant pancreatic fistula rate increased with increasing score values ( P = 0.002 and P = 0.028, respectively). Using a score cut-off value of six points, patients with a score ≥6 were considered to be at high risk. Conclusions: Body mass index >24 kg/m, a Wirsung duct size <3 mm, and preoperative diagnosis represented the preoperative factors related to a soft pancreas. These factors proved useful in the building of a risk score model to predict the incidence of pancreatic fistula. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic distal pancreatectomy was proposed as an oncologically safe approach for pancreatic ductal adenocarcinoma. Methods: A systematic review of the studies comparing laparoscopic and open distal pancreatectomy was conducted. The primary endpoint was an R0 resection rate. The secondary endpoints were intra- and postoperative results, tumour size, mean harvested lymph node, number of patients eligible for adjuvant therapy and overall survival. Results: Five comparative case control studies involving 261 patients (30.7 % laparoscopic and 69.3 % open) who underwent a distal pancreatectomy were included. The R0 resection rate was similar between the two groups ( P = 0.53). The laparoscopic group had longer operative times ( P = 0.04), lesser blood loss ( P = 0.01), a shorter hospital stay ( P < 0.001) and smaller tumour size ( P = 0.04) as compared with the laparotomic group. Overall morbidity, postoperative pancreatic fistula, reoperation, mortality and number of patients eligible for adjuvant therapy were similar. The mean harvested lymph nodes were comparable in the two groups ( P = 0.33). The laparoscopic approach did not affect the overall survival rate ( P = 0.32). Conclusion: Even if the number of patients compared is underpowered, the laparoscopic approach in the treatment of PDAC seems to be safe and efficacious. However, additional prospective, randomised, multicentric trials are needed to correctly evaluate the laparoscopic approach in PDAC. [ABSTRACT FROM AUTHOR]

Background: Whether patients with small (<2 cm), sporadic nonfunctioning pancreatic endocrine tumors (NF-PETs) should directly undergo pancreatic surgery or should be followed longitudinally to detect growth and malignancy still has to be defined. Study Design: Based on the pertinent literature of the past decade, a Markov model was developed to investigate this issue. In the wait-and-see strategy arm, surgery was performed if the tumor attained a size ≥2 cm or surpassed 20% of the initial size. In a Monte Carlo probabilistic analysis, 100 hypothetical patients undergoing a wait-and-see strategy were compared to 100 patients directly undergoing surgery, with the aim of investigating the efficacy and cost-effectiveness of the two strategies. Results: During the postdiagnostic lifetime, 63 NF-PETs in the wait-and-see group showed significant growth and underwent surgery: 38 were stage I, 10 were stage II, 15 were stage III and none were stage IV. In the base-case scenario, the mean life expectancy and quality-adjusted life expectancy were found to be superior after immediate surgery [26.1 years and 11.8 quality-adjusted life years (QALYs)] than with the wait-and-see strategy (22.1 years and 8.3 QALYs) as the consequence of ageing during the wait-and-see follow-up which increased mortality due to surgery, when surgery was needed. The model was sensitive to starting age and length of follow-up; in particular, for patients >65 years of age, the two strategies provided similar results but the wait-and-see strategy was more cost-effective. Conclusions: The wait-and-see strategy for NF-PETs <2 cm represents a reasonable approach in patients over 65 years of age; otherwise, immediate surgery is preferable. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: The factors related to the learning curve for laparoscopic distal pancreatectomy have rarely been evaluated. Methods: A retrospective study of 32 patients who underwent a laparoscopic distal pancreatectomy performed at a high-volume center by a single pancreatic surgeon experienced with laparoscopic surgery was conducted. Pre-, intra- and postoperative data were collected. The primary endpoint was the length of the operation. The secondary endpoints were the conversion and reoperation rates, overall postoperative morbidity and mortality rates, the length of hospital stay and rate of unplanned splenectomy. Results: The length of the operation and the cumulative sum of the procedures presented a logarithmic correlation ( P = 0.048). The learning curve appeared to have been completed after 17 procedures ( P = 0.040). The multivariate analysis confirmed that the completion of the learning curve (CLC) reduced the length of the operation by 18 % ( P = 0.009), but extended resection increased the length of the operation ( P = 0.023). The conversion and reoperation rates, overall postoperative morbidity and mortality rates and length of the hospital stay were not related to the CLC. Unplanned splenectomy was more frequently performed during the first 17 procedures. Conclusions: The length of the operation seems to be the main factor related to the CLC for laparoscopic distal pancreatectomy. The learning curve could be considered to be completed after about 17 procedures if performed by surgeons experienced with laparoscopic techniques at high-volume centers. [ABSTRACT FROM AUTHOR]

We analyzed the interactions between human primary cells from pancreatic ductal adenocarcinoma (PDAC) and polymeric scaffolds to develop 3D cancer models useful for mimicking the biology of this tumor. Three scaffold types based on two biocompatible polymeric formulations, such as poly(vinyl alcohol)/gelatin (PVA/G) mixture and poly (ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) copolymer, were obtained via different techniques, namely, emulsion and freeze-drying, compression molding followed by salt leaching, and electrospinning. In this way, primary PDAC cells interfaced with different pore topographies, such as sponge-like pores of different shape and size or nanofiber interspaces. The aim of this study was to investigate the influence played by the scaffold architecture over cancerous cell growth and function. In all scaffolds, primary PDAC cells showed good viability and synthesized tumor-specific metalloproteinases (MMPs) such as MMP-2, and MMP-9. However, only sponge-like pores, obtained via emulsion-based and salt leaching-based techniques allowed for an organized cellular aggregation very similar to the native PDAC morphological structure. Differently, these cell clusters were not observed on PEOT/PBT electrospun scaffolds. MMP-2 and MMP-9, as active enzymes, resulted to be increased in PVA/G and PEOT/PBT sponges, respectively. These findings suggested that spongy scaffolds supported the generation of pancreatic tumor models with enhanced aggressiveness. In conclusion, primary PDAC cells showed diverse behaviors while interacting with different scaffold types that can be potentially exploited to create stage-specific pancreatic cancer models likely to provide new knowledge on the modulation and drug susceptibility of MMPs. [ABSTRACT FROM AUTHOR]

The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating bone stem cells to decrease the disadvantages of traditional tissue grafts. However, the effective clinical application of tissue-engineered bone is limited by insufficient neovascularization. As bone is a highly vascularized tissue, new strategies to promote both osteogenesis and vasculogenesis within the scaffolds need to be considered for a successful regeneration. It has been demonstrated that bone and blood vases are piezoelectric, namely, electric signals are locally produced upon mechanical stimulation of these tissues. The specific effects of electric charge generation on different cells are not fully understood, but a substantial amount of evidence has suggested their functional and physiological roles. This review summarizes the special contribution of piezoelectricity as a stimulatory signal for bone and vascular tissue regeneration, including osteogenesis, angiogenesis, vascular repair, and tissue engineering, by considering different stem cell sources entailed with osteogenic and angiogenic potential, aimed at collecting the key findings that may enable the development of successful vascularized bone replacements useful in orthopedic and otologic surgery. [ABSTRACT FROM AUTHOR]

Aim. To identify factors related to survival in patients affected by well-differentiated PETs (benign, uncertain behavior, and carcinoma) who underwent R0 pancreatic resection. Methods. Retrospective study of 74 consecutive patients followed up from January 1980 to December 2011. Prognostic factors were sex, age, type of tumor, presence of symptoms, type of surgical procedure, size of tumor, lymph nodes status, WHO classification, and TNM stage. Overall survival was evaluated using the Kaplan-Meier method. Cox regression analyses were used to identify the factors associated with prognosis in univariate andmultivariate analysis. Results. The mean follow-up of all the patients was 106 ± 89 months. The 5-10-year long-term survival was 90.9% and 79.1%, respectively. At univariate analysis, patient age <55 years was significantly related to a better long-term survival compared to patients age =55 years (307 ± 15 months versus 192 ± 25 months; P = 0.010). Multivariate analysis showed that female gender (P = 0.006), patients without comorbidities (P = 0.033), and patients affected by well-differentiated benign pancreatic endocrine tumors (P = 0.008 and P = 0.002 in relation to tumors with uncertain behavior and carcinomas, resp.) were factors significantly related to a better long-term survival. Conclusions. Patients factors were strongly related to a better long-term survival in patients observed.WHO classification is a very useful prognostic tool for well-differentiated PETs. [ABSTRACT FROM AUTHOR]

Background: Pancreatic metastases from renal cell carcinoma are uncommon. Methods: Retrospective study of 8 patients with a diagnosis of pancreatic metastasis from renal cell carcinoma observed in our Institute. Results: Patients were 6 (75%) males and 2 (25%) females. Mean age was 65.3 years. In 5 patients (57.1%), symptoms were present. The median interval of onset from nephrectomy was 10 years. No cases of synchronous pancreatic metastases were observed. Surgical resection was performed in 7 (87.5%) patients. At pathological examination, solitary metastases were identified in 5 patients (71.4%). No post-operative mortality was observed; the morbidity rate was 42.8%. In the group of patients who underwent pancreatic resection, median overall survival was 43.0 months (range 12.9–74.5), median disease-free survival was 23.6 months (range 9.9–74.5). Conclusions: Pancreatic metastasis from renal cell carcinoma typically occurs after a long period from the initial nephrectomy, and seems to be related to a good prognosis. [ABSTRACT FROM AUTHOR]

Advanced ductal pancreatic carcinoma (PC) remains a challenge for current surgical and medical approaches. It has recently been claimed that radiofrequency ablation (RFA) may be beneficial for patients with locally advanced or metastatic PC. Using the MEDLINE database, we found seven studies involving 106 patients in which PC was treated using RFA. The PC was mainly located in the pancreatic head (66.9%) with a median size of 4.6 cm. RFA was carried out in 85 patients (80.1%) with locally advanced PC and in 21 (19.9%) with metastatic disease. Palliative surgical procedures were carried out in 41.5% of the patients. The average temperature used was 90 °C (with a temperature range of 30-105 °C) and the ratio between the number of passes of the probe and the size of the tumor in centimeters was 0.5 (range of 0.36-1). The median postoperative morbidity and mortality were 28.3% and 7.5%, respectively; the median survival was 6.5 months (range of 1-33 months). In conclusion, RFA is a feasible technique: however, its safety and long-term results are disappointing; Thus, the RFA procedure should not be recommended in clinical practice for a PC patient. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the clinical relevance of the World Health Organization (WHO) and tumor node metastasis (TNM) classifications in patients affected by pancreatic endocrine tumors. Data from 76 consecutive patients with pancreatic endocrine tumors who underwent surgery were analyzed. Well-differentiated tumors were observed more frequently (57.9%) than well or poorly differentiated carcinomas (26.3% and 15.8%, respectively). The TNM stage was I in 27.6%, II in 39.5%, III in 19.7%, and IV in 13.2%. Univariate analysis of disease-specific survival showed that patients with stages I–II had a significantly better survival rate than those with stages III–IV (hazard ratio (HR), 12.46; 95% confidence interval (CI), 1.53–101.32; P = 0.018; HR, 25.74; 95% CI, 3.07–216.07; P = 0.003, respectively). Regarding the WHO classification, poorly differentiated carcinomas had the worst prognosis (HR, 79.13; 95% CI, 9.99–626.60; P < 0.001). Multivariate Cox regression analysis of disease-specific survival showed that the WHO classification is the only independent factors of improved survival: both poorly and well-differentiated carcinomas had an increased risk of death compared with WDTs (HR, 100.42; 95% CI, 12.16–829.40; P < 0.001; HR, 10.73; 95% CI, 1.12–104.17; P = 0.040, respectively). TNM classification and the WHO system are highly correlated ( P < 0.001). TNM stage and the WHO classification seems to be equally reliable, even if TNM classification tends to understage the patients classified using the WHO system. [ABSTRACT FROM AUTHOR]

Patients with unresectable locally advanced pancreatic cancer remain a challenge for current surgical and medical approaches; the overall survival rate of these patients is poor, only 3-6 months in patients with unresectable disease due to locally advanced cancer and metastatic disease, respectively. Using currently available surgical techniques, patients affected by locally advanced pancreatic adenocarcinoma are at high risk for positive margin resection and R1 or R2 resectional surgery; chemoradiation generally determines a minimal symptomatic improvement. Trials of chemotherapy with or without radiotherapy have shown some improvement in symptoms and quality of life, without significant improvement in survival. Thus, radiofrequency ablation (RFA) has emerged in recent years as a potential curative approach in these kinds of patients. In this paper, we will review the results of RFA in pancreatic adenocarcinoma on the basis of recent literature considering the feasibility of the technique, its safety, efficacy and its long term results. In brief, all studies demonstrate that the technique is feasible and should be carried out using instrumentation guided by ultrasound. The safety of RFA in pancreatic cancer is under debate as are the long-term results of the technique. [ABSTRACT FROM AUTHOR]

Cosmetics has recently focused on biobased skin-compatible materials. Materials from natural sources can be used to produce more sustainable skin contact products with enhanced bioactivity. Surface functionalization using natural-based nano/microparticles is thus a subject of study, aimed at better understanding the skin compatibility of many biopolymers also deriving from biowaste. This research investigated electrospray as a method for surface modification of cellulose tissues with chitin nanofibrils (CNs) using two different sources—namely, vegetable (i.e., from fungi), and animal (from crustaceans)—and different solvent systems to obtain a biobased and skin-compatible product. The surface of cellulose tissues was uniformly decorated with electrosprayed CNs. Biological analysis revealed that all treated samples were suitable for skin applications since human dermal keratinocytes (i.e., HaCaT cells) successfully adhered to the processed tissues and were viable after being in contact with released substances in culture media. These results indicate that the use of solvents did not affect the final cytocompatibility due to their effective evaporation during the electrospray process. Such treatments did not also affect the characteristics of cellulose; in addition, they showed promising anti-inflammatory and indirect antimicrobial activity toward dermal keratinocytes in vitro. Specifically, cellulosic substrates decorated with nanochitins from shrimp showed strong immunomodulatory activity by first upregulating then downregulating the pro-inflammatory cytokines, whereas nanochitins from mushrooms displayed an overall anti-inflammatory activity via a slight decrement of the pro-inflammatory cytokines and increment of the anti-inflammatory marker. Electrospray could represent a green method for surface modification of sustainable and biofunctional skincare products. [ABSTRACT FROM AUTHOR]

We present the results of an investigation of a highly variable C iv broad absorption line (BAL) feature in spectra of the quasar SBS 1408+544 (z = 2.337) that shows a significant shift in velocity over time. This source was observed as a part of the Sloan Digital Sky Survey (SDSS) Reverberation Mapping project and the SDSS-V Black Hole Mapper Reverberation Mapping project, and has been included in two previous studies, both of which identified significant variability in a high-velocity C iv BAL on timescales of just a few days in the quasar rest frame. Using ∼130 spectra acquired over 8 yr of spectroscopic monitoring with SDSS, we have determined that this BAL is not only varying in strength, but is also systematically shifting to higher velocities. Using cross-correlation methods, we measure the velocity shifts (and corresponding acceleration) of the BAL over a wide range of timescales, measuring an overall velocity shift of Δ v = − 683 − 84 + 89 km s−1 over the 8 yr monitoring period. This corresponds to an average rest-frame acceleration of a = 1.04 − 0.13 + 0.14 cm s−2, though the magnitude of the acceleration on shorter timescales is not constant throughout. We place our measurements in the context of BAL-acceleration models and examine various possible causes of the observed velocity shift. [ABSTRACT FROM AUTHOR]

A fundamental goal of modern-day astrophysics is to understand the connection between supermassive black hole (SMBH) growth and galaxy evolution. Merging galaxies offer one of the most dramatic channels for galaxy evolution known, capable of driving inflows of gas into galactic nuclei, potentially fueling both star formation and central SMBH activity. Dual active galactic nuclei (dual AGNs) in late-stage mergers with nuclear pair separations <10 kpc are thus ideal candidates to study SMBH growth along the merger sequence since they coincide with the most transformative period for galaxies. However, dual AGNs can be extremely difficult to confirm and study. Hard X-ray (>10 keV) studies offer a relatively contamination-free tool for probing the dense obscuring environments predicted to surround the majority of dual AGN in late-stage mergers. To date, only a handful of the brightest and closest systems have been studied at these energies due to the demanding instrumental requirements involved. We demonstrate the unique capabilities of HEX-P to spatially resolve the soft and -- for the first time -- hard X-ray counterparts of closely-separated (~2" -- 5") dual AGNs in the local Universe. By incorporating physically-motivated obscuration models, we reproduce realistic broadband X-ray spectra expected for deeply embedded accreting SMBHs. Hard X-ray spatially resolved observations of dual AGNs -- accessible only to HEX-P -- wiU hence transform our understanding of dual AGN in the nearby Universe. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasia, characterized by early metastasis, low diagnostic rates at early stages, resistance to drugs, and poor prognosis. There is an urgent need to better characterize this disease in order to identify efficient diagnostic/prognostic biomarkers. Since microRNAs (miRNAs) contribute to oncogenesis and metastasis formation in PDAC, they are considered potential candidates for fulfilling this task. In this work, the levels of two miRNA subsets (involved in chemoresistance or with oncogenic/tumor suppressing functions) were investigated in a panel of PDAC cell lines and liquid biopsies of a small cohort of patients. We used RT-qPCR and droplet digital PCR (ddPCR) to measure the amounts of cellular- and vesicle-associated, and circulating miRNAs. We found that both PDAC cell lines, also after gemcitabine treatment, and patients showed low amounts of cellular-and vesicle-associated miR-155-5p, compared to controls. Interestingly, we did not find any differences when we analyzed circulating miR-155-5p. Furthermore, vesicle-related miR-27a-3p increased in cancer patients compared to the controls, while circulating let-7a-5p, miR-221-3p, miR-23b-3p and miR-193a-3p presented as dysregulated in patients compared to healthy individuals. Our results highlight the potential clinical significance of these analyzed miRNAs as non-invasive diagnostic molecular tools to characterize PDAC. [ABSTRACT FROM AUTHOR]

Changing-look active galactic nuclei (AGNs) present an important laboratory to understand the origin and physical properties of the broad-line region (BLR). We investigate follow-up optical spectroscopy spanning ∼500 days after the outburst of the changing-look AGN 1ES 1927+654. The emission lines displayed dramatic, systematic variations in intensity, velocity width, velocity shift, and symmetry. Analysis of optical spectra and multiband images indicates that the host galaxy contains a pseudobulge and a total stellar mass of 3.56 âˆ' 0.35 + 0.38 Ă— 10 9 M ⊙ . Enhanced continuum radiation from the outburst produced an accretion disk wind, which condensed into BLR clouds in the region above and below the temporary eccentric disk. Broad Balmer lines emerged ∼100 days after the outburst, together with an unexpected, additional component of narrow-line emission. The newly formed BLR clouds then traveled along a similar eccentric orbit (e ≈ 0.6). The Balmer decrement of the BLR increased by a factor of ∼4â€"5 as a result of secular changes in cloud density. The drop in density at late times allowed the production of He i and He ii emission. The mass of the black hole cannot be derived from the broad emission lines because the BLR is not virialized. Instead, we use the stellar properties of the host galaxy to estimate M BH = 1.38 âˆ' 0.66 + 1.25 Ă— 10 6 M ⊙ . The nucleus reached near or above its Eddington limit during the peak of the outburst. We discuss the nature of the changing-look AGN 1ES 1927+654 in the context of other tidal disruption events. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have reported worse outcomes of converted laparoscopic distal pancreatectomy (CLDP) with respect to total laparoscopic (TLDP) and open (ODP). The aim of the study was to evaluate the impact of conversion on patient outcome and on total cost. Methods: Patients requiring a conversion (CLDP) were compared with both TLDP and ODP patients. The relevant patient- and tumour-related variables were collected for each patient. Both intra and postoperative data were extracted. Propensity score matching (PSM) analysis was carried out to equate the groups compared. Results: Two hundred and five patients underwent DP, 105 (51.2%) ODPs, 81 (39.5%) TLDPs, and 19 (9.3%) CLDPs. After PSM, 19 CLDPs, 38 TLDPs, and 38 ODPs were compared. Patients who underwent CLDP showed a significantly longer operative time (P < 0.001), and an increase in blood loss (P = 0.032) and total cost (P = 0.034) with respect to TLDP, and a significantly longer operative time (P < 0.001), less frequent postoperative morbidity (P = 0.050), and a higher readmission rate (P = 0.035) with respect to ODP. Conclusion: Total laparoscopic pancreatectomy was superior regarding operative findings and total costs with respect to CLDP; ODP showed a higher postoperative morbidity rate and a lower readmission rate with respect to CLDP. However, the reasons for the readmission of patients who underwent CLDP were mainly related to postoperative pancreatic fistula (POPF) grade B which is usually due to pancreas texture. Thus, the majority of distal pancreatectomies can be started using a minimally invasive approach, performing an early conversion if necessary. [ABSTRACT FROM AUTHOR]