Cholecalciferol complexation with hydroxypropyl-ß-cyclodextrin (HPBCD) and its molecular dynamics simulation.

The focus of the current study is to investigate cholecalciferol (vitamin D3) solubilization by hydroxypropyl-ß-cyclodextrin (HPBCD) complexation through experimental and computational studies. Phase solubility diagram of vitamin D3 (completely insoluble in water) has an AP profile revealing a deviation from a linear regression with HPBCD concentration increase. Differential scanning calorimetry (DSC) is the best tool to confirm complex formation by disappearance of cholecalciferol exothermic peak in cholecalciferol-HPBCD complex thermogram, due to its amorphous state by entering HPBCD inner hydrophobic cavity, similarly validated by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). AP solubility diagram profile can be associated with cholecalciferol-HPBCD complex instability in liquid phase requiring spray drying to bring it to a solid dispersion state (always more stable) illustrated by scanning electron microscopy (SEM). Computational studies led to a deeper understanding and clarification, at molecular level, of the interactions within cholecalciferol-HPBCD complex. Thermodynamics and geometry of the complex were investigated by molecular dynamics (MD) simulation.

Diagnostic value of digital droplet polymerase chain reaction and digital multiplexed detection of single-nucleotide variants in pancreatic cytology specimens collected by EUS-guided FNA.

BACKGROUND AND AIMS: EUS-guided FNA is recommended as a first-line procedure for the histopathologic diagnosis of pancreatic cancer. Molecular analysis of EUS-FNA samples might be used as an auxiliary tool to strengthen the diagnosis. The current study aimed to evaluate the diagnostic performances of K-ras testing using droplet digital polymerase chain reaction (ddPCR) and a novel single-nucleotide variant (SNV) assay performed on pancreatic EUS-FNA samples. METHODS: EUS-FNA specimens from 31 patients with pancreatic masses (22 pancreatic ductal adenocarcinomas, 7 chronic pancreatitis, and 2 pancreatic neuroendocrine tumors) were included in the study. K-ras testing was initially performed by ddPCR. In addition, mutational status was evaluated using an SNV assay by NanoString technology, using digital enumeration of unique barcoded probes to detect 97 SNVs from 24 genes of clinical significance. RESULTS: The overall specificity and sensitivity of cytologic examination were 100% and 63%, respectively. K-ras mutation testing was performed using ddPCR, and the sensitivity increased to 87% with specificity 90%. The SNV assay detected at least 1 variant in 90% of pancreatic ductal adenocarcinoma samples; the test was able to detect 2 K-ras codon 61 mutations in 2 cases of pancreatic ductal adenocarcinoma, which were missed by ddPCR. The overall diagnostic accuracy of the cytologic examination alone was 74%, and it increased to 91% when the results of both molecular tests were considered for the cases with negative and inconclusive results. CONCLUSIONS: The current study illustrated that integration of K-ras analysis with cytologic evaluation, especially in inconclusive cases, can enhance the diagnostic accuracy of EUS-FNA for pancreatic lesions.

Micronized Zaleplon Delivery via Orodispersible Film and Orodispersible Tablets.

The following research study focuses on improving the solubility of zaleplon (BCS class II drug) via micronization technique in order to enhance its oral delivery in orodispersible formulations. Zaleplon along with a surfactant solution was micronized by ultrasonication. The micronization process reduced the particle size of the crystalline drug about six-fold from its original size of 155.5 µm. The micronized zalepon dispersion was lyophilized to allow for a change in the state of matter (to a powder). The superior dissolution parameters (Q5, Q30, IDR, MDR, MDT, DE, and RDR) of zaleplon in microcrystalline form over the original crystalline form in in vitro dissolution studies had unraveled that micronization technique is an efficient tool in enhancing drug solubility. The micronized zaleplon solid dispersion (after lyophilization) was loaded into orodispersible tablet (ODT) and orodispersible film (ODF) formulations. The positive quality of ODT with adequate hardness and smooth texture was attributing to the presence of Pearlitol Flash® as a ready to use ODT platform. On the other hand, the ODF loaded with micronized zaleplon and prepared with Lycoat® RS 720 (as a film former) ensured adequate tensile strength. The disintegration time of ODT and ODF was 30 ± 5 and 35 ± 5 s, respectively. Thus, the orodispersible formulations containing micronized zaleplon have a strong potential for rapid disintegration following superior absorption in solution state through oral cavity into the blood stream, envisaging better oral delivery.

Physicochemical and Preclinical Evaluation of a Novel Buccal Measles Vaccine.

The aim of this study is to develop an orally disintegrating film (ODF) containing a microparticulate measles vaccine formulation for buccal delivery. The measles vaccine microparticles were made with biocompatible and biodegradable bovine serum albumin (BSA) and processed by spray drying. These vaccine microparticles were incorporated in the ODF, consisting of Lycoat RS720®, Neosorb P60W® and Tween 80. The yield of the microparticles was approximately 85-95%, w/w. The mean size of the vaccine microparticles was 3.65 ± 1.89 µm and had a slightly negative surface charge of 32.65 ± 2.4 mV. The vaccine particles were nontoxic to normal cells at high concentrations (500 µg/2.5 × 105 cells) of vaccine particles. There was a significant induction of innate immune response by vaccine microparticles which was observed in vitro when compared to blank microparticles (P < 0.05). The vaccine microparticles also significantly increased the antigen presentation and co-stimulatory molecules expression on antigen presenting cells, which is a prerequisite for Th1 and Th2 immune responses. When the ODF vaccine formulation was dosed in juvenile pigs, significantly higher antibody titers were observed after week 2, with a significant increase at week 4 and plateauing through week 6 comparative to naïve predose titers. The results suggest that the ODF measles vaccine formulation is a viable dosage form alternative to noninvasive immunization that may increase patient compliance and commercial distribution.

Taste Masking of Griseofulvin and Caffeine Anhydrous Using Kleptose Linecaps DE17 by Hot Melt Extrusion.

The objective of this project was to investigate the potential of Kleptose Linecaps DE17 (KLD) in masking the unpleasant/bitter taste of therapeutic agents by hot melt extrusion (HME). Griseofulvin (GRI) and caffeine anhydrous (CA) were used as a bitter active pharmaceutical ingredient (API) model drugs. Thermogravimetric studies confirmed the stability of GRI, CA, and KLD at the employed extrusion temperatures. The differential scanning calorimetry (DSC) studies revealed a characteristic melting endotherm of GRI at 218-220°C and CA at 230-232°C in the physical mixtures as well as in all extrudates over the period of study, indicating the crystalline nature of drug. HME of KLD was achieved only in the presence of plasticizer. Among the several plasticizers investigated, xylitol showed improved processability of KLD at 15% w/w concentration. Dissolution studies of HME extrudates using simulated salivary medium exhibited ∼threefold less release compared to physical mixture at the end of 5 min (the lesser drug release, better the taste masking efficiency). Furthermore, the results from the sensory evaluation of products in human panel demonstrated strong bitter taste in the case of physical mixture compared to the HME formulation, suggesting the potential of Kleptose Linecaps DE17 as taste masking polymer in melt extruded form.

Experimental and computational studies of physicochemical properties influence NSAID-cyclodextrin complexation.

The objective of this research was to investigate physicochemical properties of an active pharmaceutical ingredient (API) that influence cyclodextrin complexation through experimental and computational studies. Native ß-cyclodextrin (B-CD) and two hydroxypropyl derivatives were first evaluated by conventional phase solubility experiments for their ability to complex four poorly water-soluble nonsteroidal anti-inflammatory drugs (NSAIDs). Differential scanning calorimetry was used to confirm complexation. Secondly, molecular modeling was used to estimate Log P and aqueous solubility (S o) of the NSAIDs. Molecular dynamics simulations (MDS) were used to investigate the thermodynamics and geometry of drug-CD cavity docking. NSAID solubility increased linearly with increasing CD concentration for the two CD derivatives (displaying an AL profile), whereas increases in drug solubility were low and plateaued in the B-CD solutions (type B profile). The calculated Log P and S o of the NSAIDs were in good concordance with experimental values reported in the literature. Side chain substitutions on the B-CD moiety did not significantly influence complexation. Explicitly, complexation and the associated solubility increase were mainly dependent on the chemical structure of the NSAID. MDS indicated that each NSAID-CD complex had a distinct geometry. Moreover, complexing energy had a large, stabilizing, and fairly constant hydrophobic component for a given CD across the NSAIDs, while electrostatic and solvation interaction complex energies were quite variable but smaller in magnitude.

Active Cellulose-Based Food Packaging and Its Use on Foodstuff.

The essential role of active packaging is food quality improvement, which results in an extension of shelf life. Active packaging can also further enhance distribution from the origin point, and contributes to food waste reduction, offering greater sustainability. In this study, we introduced a new method for obtaining cellulose-based active packages, combining gamma irradiation as an eco-friendly activation process, and clove essential oil and cold-pressed rosehip seed oil as bioactive agents. Newly obtained bioactive materials were evaluated to assess their structural, hydrophobic, and morphological properties, thermal stability, and antioxidant and antimicrobial properties. The results showed that the plant oils induced their antimicrobial effects on paper, using both in vitro tests, against several bacterial strains (Gram-positive bacteria Listeria monocytogenes and Gram-negative bacteria Salmonella enteritidis and Escherichia coli), and in vivo tests, on fresh cheese curd and beef. Moreover, these oils can help control foodborne pathogens, which leads to extended shelf life.

Multicenter randomized controlled trial comparing the performance of 22 gauge versus 25 gauge EUS-FNA needles in solid masses.

BACKGROUND AND AIMS: Few randomized studies have assessed the clinical performance of 25-gauge (25G) needles compared with 22-gauge (22G) needles during endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy of intra-abdominal lesions. We aimed to compare the diagnostic yield, as well as performance characteristics of 22G versus 25G EUS biopsy needles by determining their diagnostic capabilities, the number of needle passes as well as cellularity of aspirated tissue specimen. METHODS: The study is a prospective, randomized, multicenter study. Patients were referred between January 2009 and January 2010 for diagnostic EUS including EUS-guided FNA of different lesions adjacent to the upper GI tract. All patients were randomized to EUS-FNA performed with either a 22G or 25G aspiration needle. RESULTS: EUS-FNA was performed in 135 patients (62 patients with a 22G needle). Sensitivity and specificity of the 22G needle was 94.1% and 95.8%, respectively, and for the 25G needle 94.1% and 100%, respectively. Investigators reported better visualization and performance for the 22G needle compared to the 25G (p < 0.0001). The number of tissue slides obtained was higher for the 22G needle during the second and third needle passes (p < 0.05). We did not observe significant differences between the number and preservation status of obtained cells (p > 0.05). CONCLUSIONS: A significant difference was found between the two types of needles in terms of reduced visualization of the 25G needle and suboptimal performance rating. However, this did not impact on overall results since both needles were equally successful in terms of a high diagnostic yield and overall accuracy.

Simultaneous couch and gantry dynamic arc rotation (CG-Darc) in the treatment of breast cancer with accelerated partial breast irradiation (APBI): a feasibility study.

The purpose of this study was to compare the dosimetry of CG-Darc with three-dimensional conformal radiation therapy (3D CRT) and volumetric-modulated arc therapy (RapidArc) in the treatment of breast cancer with APBI. CG-Darc plans were generated using two tangential couch arcs combined with a simultaneous noncoplanar gantry arc. The dynamic couch arc was modeled by consecutive IMRT fields at 10° intervals. RapidArc plans used a single partial arc with an avoidance sector, preventing direct beam exit into the thorax. CG-Darc and RapidArc plans were compared with 3D CRT in 20 patients previously treated with 3D CRT (group A), and in 15 additional patients who failed the dosimetric constraints of the Canadian trial and of NSABP B-39/RTOG 0413 for APBI (group B). CG-Darc resulted in superior target coverage compared to 3D CRT and RapidArc (V95%: 98.2% vs. 97.1% and 95.7%). For outer breast lesions, CG-Darc and RapidArc significantly reduced the ipsilateral breast V50% by 8% in group A and 15% in group B (p < 0.05) as compared with 3D CRT. For inner and centrally located lesions, CG-Darc resulted in significant ipsilateral lung V10% reduction when compared to 3D CRT and RapidArc (10.7% vs. 12.6% and 20.7% for group A, and 15.1% vs. 25.2% and 27.3% for group B). Similar advantage was observed in the dosimetry of contralateral breast where the percent maximum dose for CG-Darc, 3D CRT, and RapidArc were 3.9%, 6.3%, and 5.8% for group A and 4.3%, 9.2%, and 6.3% for group B, respectively (p < 0.05). CG-Darc achieved superior target coverage while decreasing normal tissue dose even in patients failing APBI dose constraints. Consequently, this technique has the potential of expanding the use of APBI to patients currently ineligible for such treatment. Modification of the RapidArc algorithm will be necessary to link couch and gantry rotation with variable dose rate and, therefore, enable the use of CG-Darc in clinical practice.

Stability of benzocaine formulated in commercial oral disintegrating tablet platforms.

Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography-mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions.

Particleboards Bonded by an Imidazole-Based Adhesive System.

Particleboards with different combinations of the adhesive material imidazole, citric acid, and sorbitol were produced. Softwood sawdust from a Swedish sawmill was mixed with an aqueous solution of the chemicals and then dried to 0% moisture content prior to pressing. The boards were pressed to a target density of 700 kg m-3 at either 200 °C or 220 °C for 10 min. The hygroscopic and mechanical properties of the boards were clearly better at 220 °C than 200 °C for all used chemical combinations. A combination of imidazole (14.4 wt%) and citric acid (11.3 wt%) led to the best results, where the thickness swelling after 24 h of water immersion was 6.3% and the internal bonding strength was 0.57 MPa. The modulus of rupture and modulus of elasticity were 3.3 MPa and 1.1 GPa, respectively. Cyclic accelerated weathering showed exceptional stability with a thickness change after boiling and drying of only 2.1% compared to the initial dry thickness. This study indicates that the presence of imidazole leads to greatly improved hygroscopic properties and good internal bonding strength when used in particleboards.

Dual domestications and origin of traits in grapevine evolution.

We elucidate grapevine evolution and domestication histories with 3525 cultivated and wild accessions worldwide. In the Pleistocene, harsh climate drove the separation of wild grape ecotypes caused by continuous habitat fragmentation. Then, domestication occurred concurrently about 11,000 years ago in Western Asia and the Caucasus to yield table and wine grapevines. The Western Asia domesticates dispersed into Europe with early farmers, introgressed with ancient wild western ecotypes, and subsequently diversified along human migration trails into muscat and unique western wine grape ancestries by the late Neolithic. Analyses of domestication traits also reveal new insights into selection for berry palatability, hermaphroditism, muscat flavor, and berry skin color. These data demonstrate the role of the grapevines in the early inception of agriculture across Eurasia.

Effects of Biological and Chemical Degradation on the Properties of Scots Pine Wood-Part I: Chemical Composition and Microstructure of the Cell Wall.

Research on new conservation treatment for archaeological wood requires large amounts of wooden material. For this purpose, artificial wood degradation (biological-using brown-rot fungus Coniophora puteana, and chemical-using NaOH solution) under laboratory conditions was conducted to obtain an abundance of similar samples that mimic naturally degraded wood and can serve for comparative studies. However, knowledge about its properties is necessary to use this material for further study. In this study, the chemical composition and microstructure of degraded cell walls were investigated using FT-IR, XRD, helium pycnometry and nitrogen absorption methods. The results show that biological degradation caused the loss of hemicelluloses and celluloses, including the reduction in cellulose crystallinity, and led to lignin modification, while chemical degradation mainly depleted the amount of hemicelluloses and lignin, but also affected crystalline cellulose. These changes affected the cell wall microstructure, increasing both surface area and total pore volume. However, the chemical degradation produced a greater number of mesopores of smaller size compared to fungal decomposition. Both degradation processes weakened the cell wall's mechanical strength, resulting in high shrinkage of degraded wood during air-drying. The results of the study suggest that degraded wood obtained under laboratory conditions can be a useful material for studies on new consolidants for archaeological wood.

Quantitative contrast-enhanced endoscopic ultrasound in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors: can we predict survival using perfusion parameters? A pilot study.

AIM: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) parameters may be used to predict prognosis of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET). The aim of this study was to investigate the association between several perfusion parameters on CEH-EUS performed before treatment and survival outcome in patients with PDAC or pNET. MATERIAL AND METHODS: Thirty patients with PDAC or pNET who underwent CEH-EUS and EUS-guided fine needle aspiration (EUS-FNA) were included. Quantitative analysis of tumor vascularity was performed using time-intensity curve (TIC) analysis-derived parameters, obtained from processing CEH-EUS recordings with a commercially available software (VueBox). Cox proportional hazards models were used to determine associations with survival outcome. RESULTS: Median overall survival (OS) for PDAC patients was 9.61 months (95% CI: 0.1-38.7) while the median OS for pNET patients was 15.81 months (95% CI: 5.8-24.75. In a multivariate model for OS, a lower peak enhancement (HR=1.76, p=0.02) and a lower wash-in area under the curve (HR=1.06, p=0.001) were associated with worse survival outcome for patients with PDAC. CONCLUSIONS: CEH-EUS parameters may be used as a surrogate to predict PDAC aggressiveness and survival before treatment. After validation by large-scale studies, CEH-EUS perfusion parameters have the potential to be used in pretreatment risk stratification of patients with PDAC and in evidence-based clinical decision support.

Technical Performance, Overall Accuracy and Complications of EUS-Guided Interventional Procedures: A Dynamic Landscape.

Endoscopic ultrasound (EUS) gained wide acceptance as the diagnostic and minimally invasive therapeutic approach for intra-luminal and extraluminal gastrointestinal, as well as various non-gastrointestinal lesions. Since its introduction, EUS has undergone substantial technological advances. This multi-centric study is a retrospective analysis of a prospectively maintained database of patients who underwent EUS for the evaluation of lesions located within the gastrointestinal tract and the proximal organs. It aimed to extensively assess in dynamic the dual-center EUS experience over the course of the past 20 years. Hence, we performed a population study and an overall assessment of the EUS procedures. The performance of EUS-FNA/FNB in diagnosing pancreatic neoplasms was evaluated. We also investigated the contribution of associating contrast-enhanced ultrasound imaging (CE-EUS) with EUS-FNA/FNB for differentiating solid pancreatic lesions or cystic pancreatic lesions. A total of 2935 patients undergoing EUS between 2002-2021 were included, out of which 1880 were diagnostic EUS and 1052 EUS-FNA/FNB (80% FNA and 20% FNB). Therapeutic procedures performed included endoscopic transmural drainage of pancreatic fluid collections, celiac plexus block and neurolysis, while diagnostic EUS-like CE-EUS (20%) and real-time elastography (12%) were also conducted. Most complications occurred during the first 7 days after EUS-FNA/FNB or pseudocyst drainage. EUS and the additional tools have high technical success rates and low rates of complications. The EUS methods are safe, cost effective and indispensable for the diagnostic or therapeutic management in gastroenterological everyday practice.

How specific molecular-targeted agents can make obsolete a 'one size fits all' approach in EGFR-mutated NSCLC treatment (Review).

Despite many advances in the latest period, lung cancer remains the cancer with the highest mortality. The latest developments concerning lung cancer treatment have changed the clinical practice by prolonging patient survival; however, unfortunately, there remains a high mortality rate firstly due to disease aggressivity and secondly through lack of early diagnosis and screening programs. Currently, researchers and clinicians are talking about personalized cancer treatment, and a complete diagnostic evaluation should consider, in addition to staging and histology, molecular aberrations, and genetics of the tumor tissue. The development of tyrosine kinase inhibitors (TKIs) has led to an improvement in survival for patients with EGFR mutations, this being the most studied driver mutation in adenocarcinoma; and at the same time an important predictive factor for patient outcome following the treatment with TKIs. Reseach must investigate the different TKI combination strategies in order to overcome resistance and to increase patient survival. Currently, there are ongoing clinical trials that will probably change the therapeutic approach for EGFR-mutated advanced or metastatic NSCLC patients.

Factors That Affect the Mechanical Strength of Archaeological Wood-A Case Study of 18th-Century Wooden Water Pipes from Bóznicza Street in Poznan, Poland.

Large amounts of archaeological wood are often excavated during groundworks in cities and towns. Part of the unearthed artefacts is usually saved, conserved and then presented in museums. However, if the finding contains several similar objects, some of them could potentially be further employed for some other practical purposes. The research aimed to determine the mechanical performance of the remains of wooden water mains excavated at Bóznicza street in Poznan, Poland and evaluate its potential usefulness for any practical purposes. First, wood density was determined along with its mechanical strength in compression. The density of archaeological wood identified as Scots pine was lower than contemporary pinewood (383 kg × m-3 vs. 572 kg × m-3); therefore, its mechanical properties in compression tests were also lower, as expected, making the wood unsuitable for any practical applications. However, the differences in modulus of elasticity and compressive strength were not justified by the differences in wood density. Further infrared spectroscopy and X-ray diffraction analyses revealed additional differences in chemical composition and cellulose crystallinity between archaeological and contemporary wood. The results indicated the decrease in carbohydrate content and cellulose crystallinity in degraded wood, which, in addition to wood density, apparently contribute to the deterioration in mechanical strength of archaeological wood. The case study of the excavated archaeological wooden pipes shows that they have historical value but are not useful for practical purposes. It also revealed that not only wood density but also its chemical composition and cellulose crystallinity level has a substantial impact on the wood mechanical properties, particularly in compression.

Real-time computer-aided diagnosis of focal pancreatic masses from endoscopic ultrasound imaging based on a hybrid convolutional and long short-term memory neural network model.

Differential diagnosis of focal pancreatic masses is based on endoscopic ultrasound (EUS) guided fine needle aspiration biopsy (EUS-FNA/FNB). Several imaging techniques (i.e. gray-scale, color Doppler, contrast-enhancement and elastography) are used for differential diagnosis. However, diagnosis remains highly operator dependent. To address this problem, machine learning algorithms (MLA) can generate an automatic computer-aided diagnosis (CAD) by analyzing a large number of clinical images in real-time. We aimed to develop a MLA to characterize focal pancreatic masses during the EUS procedure. The study included 65 patients with focal pancreatic masses, with 20 EUS images selected from each patient (grayscale, color Doppler, arterial and venous phase contrast-enhancement and elastography). Images were classified based on cytopathology exam as: chronic pseudotumoral pancreatitis (CPP), neuroendocrine tumor (PNET) and ductal adenocarcinoma (PDAC). The MLA is based on a deep learning method which combines convolutional (CNN) and long short-term memory (LSTM) neural networks. 2688 images were used for training and 672 images for testing the deep learning models. The CNN was developed to identify the discriminative features of images, while a LSTM neural network was used to extract the dependencies between images. The model predicted the clinical diagnosis with an area under curve index of 0.98 and an overall accuracy of 98.26%. The negative (NPV) and positive (PPV) predictive values and the corresponding 95% confidential intervals (CI) are 96.7%, [94.5, 98.9] and 98.1%, [96.81, 99.4] for PDAC, 96.5%, [94.1, 98.8], and 99.7%, [99.3, 100] for CPP, and 98.9%, [97.5, 100] and 98.3%, [97.1, 99.4] for PNET. Following further validation on a independent test cohort, this method could become an efficient CAD tool to differentiate focal pancreatic masses in real-time.

Combined contrast-enhanced power Doppler and real-time sonoelastography performed during EUS, used in the differential diagnosis of focal pancreatic masses (with videos).

BACKGROUND: Contrast-enhanced power Doppler (CEPD) and real-time sonoelastography (RTSE) performed during EUS were previously described to be useful for the differential diagnosis between chronic pseudotumoral pancreatitis and pancreatic cancer. OBJECTIVE: To prospectively assess the accuracy of the combination of CEPD and RTSE to differentiate pancreatic focal masses. DESIGN: Cross-sectional feasibility study. SETTING: A tertiary-care academic referral center. PATIENTS: The study group included 54 patients with chronic pancreatitis (n = 21) and pancreatic adenocarcinoma (n = 33). INTERVENTIONS: Both imaging methods (CEPD and RTSE) were performed sequentially during the same EUS examination. Power Doppler mode examination was performed after intravenous injection of a second-generation contrast agent (2.4 mL of SonoVue), and the data were digitally recorded, comprising both the early arterial phase and venous/late phase. Three 10-second sonoelastographic videos were also digitally recorded that included the focal mass and the surrounding pancreatic parenchyma. Postprocessing analyses based on specially designed software were used to analyze the CEPD and RTSE videos. A power Doppler vascularity index was used to characterize CEPD videos, the values being averaged during a 10-second video in the venous phase. Hue histogram analysis was used to characterize RTSE videos, with the mean hue histogram values being also averaged during a 10-second video. MAIN OUTCOME MEASUREMENTS: To differentiate chronic pancreatitis and pancreatic cancer. RESULTS: The sensitivity, specificity, and accuracy of combined information provided by CEPD and RTSE to differentiate hypovascular hard masses suggestive of pancreatic carcinoma were 75.8%, 95.2%, and 83.3%, respectively, with a positive predictive value and negative predictive value of 96.2% and 71.4%, respectively. LIMITATION: A single-center, average size of study population. CONCLUSIONS: A combination of CEPD and RTSE performed during EUS seems to be a promising method that allows characterization and differentiation of focal pancreatic masses.

EUS and cytological EUS-FNA prognostic factors in patients with unresectable pancreatic cancer receiving chemotherapy.

BACKGROUND/AIMS: The incidence of pancreatic cancer is increasing. It is usually diagnosed in an advanced stage despite the improvement in diagnostic techniques. The current study was designed to prospectively analyze several demographic and tumour related variables identified by EUS and EUS-FNA cytology that may affect survival in patients with unresectable pancreatic cancer receiving chemotherapy. METHODOLOGY: The study prospectively included 72 patients diagnosed with pancreatic cancer. Only patients without surgery were selected. All the patients received chemotherapy with the same drug (5-FU). They underwent power Doppler EUS followed by EUS-FNA in all cases. The following information obtained by EUS and EUS-FNA cytology were prepared for inclusion in multivariate survival analysis (tumour localization, portal vein invasion, power Doppler signals presence, collateral circulation, signs of chronic pancreatitis, T and N status, nuclear atypia, nuclear enlargement, pleomorphism, nuclear/cytoplasm ratio, and coarse chromatin). RESULTS: The entire included population was analyzed to identify factors affecting prognosis. The overall Cox model had a significance level of p = 0.032. There were three factors that had a major impact on the survival time of the patients: regional lymph node involvement (p = 0.029), nuclear pleomorphism (p = 0.037) and nuclear enlargement (p = 0.019). CONCLUSIONS: The current pre-treatment evaluation of the pancreatic cancer patients by EUS and EUS-FNA could offer some valuable information for appreciation of patients' future evolution. However, extensive studies are required for a complex prognosis scoring system.