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Traditional histological evaluation for grading liver disease severity is based on subjective and semi-quantitative scores. We examined the relationship between digital pathology analysis and corresponding scoring systems for the assessment of hepatic necroinflammatory activity. A prospective, multicenter study including 156 patients with chronic liver disease (74% nonalcoholic fatty liver disease-NAFLD, 26% chronic hepatitis-CH etiologies) was performed. Inflammation was graded according to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network system and METAVIR score. Whole-slide digital image analysis based on quantitative (I-score: inflammation ratio) and morphometric (C-score: proportionate area of staining intensities clusters) measurements were independently performed. Our data show that I-scores and C-scores increase with inflammation grades (p < 0.001). High correlation was seen for CH (ρ = 0.85–0.88), but only moderate for NAFLD (ρ = 0.5–0.53). I-score (p = 0.008) and C-score (p = 0.002) were higher for CH than NAFLD. Our MATLAB algorithm performed better than QuPath software for the diagnosis of low-moderate inflammation (p < 0.05). C-score AUC for classifying NASH was 0.75 (95%CI, 0.65–0.84) and for moderate/severe CH was 0.99 (95%CI, 0.97–1.00). Digital pathology measurements increased with fibrosis stages (p < 0.001). In conclusion, quantitative and morphometric metrics of inflammatory burden obtained by digital pathology correlate well with pathologists' scores, showing a higher accuracy for the evaluation of CH than NAFLD. [ABSTRACT FROM AUTHOR]

This paper documents the development of an empirically-basedsystem implemented in Prolog that automatically resolves severalkinds of anaphora in Spanish texts. These are pronominalreferences, surface-count anaphora, one-anaphora and ellipticalzero-subject constructions (i.e., sentences that omit theirpronominal subject). The resolution is based onrepresentations resulting from either partial or full parsing. Thesystem developed can also work on the output of a POStagger or with different dictionaries, without changing thegrammar. This grammar represents the syntactic information of eachlanguage by means of the Slot Unification Grammar formalism. The different kinds of information used for anaphora resolution in full and partial parsing are shown, as wellas evaluation results. The system has been adapted toEnglish texts, obtaining encouraging results that prove that itcan be applied with only a very few refinements to other languagesas well as Spanish and English. In addition, the differencesbetween English and Spanish anaphora are noted. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell tumor is a rare lymphoma, which has been included as an independent entity in the World Health Organization (WHO) 2008 classification for cutaneous lymphomas. This neoplasm usually affects middle-aged or elderly patients with predominant skin or soft tissues involvement. Although it usually has a good initial response to chemotherapy, relapses are the rule and they occur rapidly. We report a new case of an 81-year-old woman with a blastic plasmacytoid dendritic cell tumors with an unusual presentation. López V, Martí N, Ferrández A, Martín JM, Jordá E. An atypical presentation of a blastic plasmacytoid dendritic cell tumors. [ABSTRACT FROM AUTHOR]

The study of phonological proximity makes it possible to establish a basis for future decision-making in the treatment of sign languages. Knowing how close a set of signs are allows the interested party to decide more easily its study by clustering, as well as the teaching of the language to third parties based on similarities. In addition, it lays the foundation for strengthening disambiguation modules in automatic recognition systems. To the best of our knowledge, this is the first study of its kind for Costa Rican Sign Language (LESCO, for its Spanish acronym), and forms the basis for one of the modules of the already operational system of sign and speech editing called the International Platform for Sign Language Edition (PIELS). A database of 2665 signs, grouped into eight contexts, is used, and a comparison of similarity measures is made, using standard statistical formulas to measure their degree of correlation. This corpus will be especially useful in machine learning approaches. In this work, we have proposed an analysis of different similarity measures between signs in order to find out the phonological proximity between them. After analyzing the results obtained, we can conclude that LESCO is a sign language with high levels of phonological proximity, particularly in the orientation and location components, but they are noticeably lower in the form component. We have also concluded as an outstanding contribution of our research that automatic recognition systems can take as a basis for their first prototypes the contexts or sign domains that map to clusters with lower levels of similarity. As mentioned, the results obtained have multiple applications such as in the teaching area or the Natural Language Processing area for automatic recognition tasks. [ABSTRACT FROM AUTHOR]

Companies have realized the importance of "big data" in creating a sustainable competitive advantage, and user-generated content (UGC) represents one of big data's most important sources. From blogs to social media and online reviews, consumers generate a huge amount of brand-related information that has a decisive potential business value for marketing purposes. Particularly, we focus on online reviews that could have an influence on brand image and positioning. Within this context, and using the usual quantitative star score ratings, a recent stream of research has employed sentiment analysis (SA) tools to examine the textual content of reviews and categorize buyer opinions. Although many SA tools split comments into negative or positive, a review can contain phrases with different polarities because the user can have different sentiments about each feature of the product. Finding the polarity of each feature can be interesting for product managers and brand management. In this paper, we present a general framework that uses natural language processing (NLP) techniques, including sentiment analysis, text data mining, and clustering techniques, to obtain new scores based on consumer sentiments for different product features. The main contribution of our proposal is the combination of price and the aforementioned scores to define a new global score for the product, which allows us to obtain a ranking according to product features. Furthermore, the products can be classified according to their positive, neutral, or negative features (visualized on dashboards), helping consumers with their sustainable purchasing behavior. We proved the validity of our approach in a case study using big data extracted from Amazon online reviews (specifically cell phones), obtaining satisfactory and promising results. After the experimentation, we could conclude that our work is able to improve recommender systems by using positive, neutral, and negative customer opinions and by classifying customers based on their comments. [ABSTRACT FROM AUTHOR]

Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation and also in the heart. They are morphologically similar to other spindle cell, poorly differentiated sarcomas. The prognosis is poor and depends mainly on surgical options. Three cases of IS were collected from two institutions. Clinical data were retrieved and histological study was performed. A wide immunohistochemical panel was analyzed. FISH of MDM2 gene was performed, and a molecular study with NGS was implemented in all cases. The mean age of our cases was 54 years. Histologically, the tumors presented a diffuse growth pattern with heterogeneous atypical epithelioid or spindle cells and extensive thrombosed areas. All cases presented intense immunoexpression for MDM2, CDK4, CD117, c-myc, PDGFRA, and p16. PDGFRA, HTERT, and pan-TRK gained expression, while p16 lost intensity, being weaker in both the local recurrences and xenografts. The three cases showed amplification of MDM2 by FISH. NGS analysis revealed amplifications in the CDK4, PDGFRA, and KIT genes, together with BRAF mutation and KRAS amplification. P16 was expressed in all cases, losing intensity in local recurrence and xenografts. Two new alterations, a BRAF mutation and a KRAS amplification, were detected by NGS in different tumors, opening up new therapeutic options for these patients. [ABSTRACT FROM AUTHOR]

Germinotropic lymphoproliferative disorder (GLPD) is a poorly characterized lymphoproliferative entity, recently included in the World Health Organization classification of hematolymphoid neoplasms. The histological pattern of this disease comprises monotypic plasmablasts that involve the germinal centers of the lymphoid follicles (germinotrophism), forming confluent aggregates positive for both human herpes virus type 8 (HHV8) and Epstein-Barr virus. Currently, after 17 years of its first description, only 18 cases have been reported. In this article, we describe a case of a GLPD presenting in an immunocompetent 79-year-old woman with localized axillary lymphadenopathy, showing a prominent sinusoidal growth pattern, with no evidence of germinotrophism or extrasinusoidal spread. Stinking pleomorphism in tumor cells was also noted. An extension study has not revealed involvement of other groups of lymph nodes or extralymphoid sites. The patient is alive and has shown no relapse after 8 years follow-up (the longest follow-up reported period for this entity). This previously unrecognized pure sinusoidal growth pattern along with the striking pleomorphism in neoplastic cells closely mimics the appearance of an anaplastic large cell lymphoma. GLPD is not usually considered in such a setting, but it should be included in the differential diagnosis of sinusoidal proliferations. Our findings contribute to the expansion of the morphological spectrum of HHV8-associated lymphoproliferative lesions and aids in the characterization of the very infrequent GLPD entity. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients.Methods: Patients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000 mg/m2/week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300 mg/m2/week), ERL 100 mg/day and concomitant radiotherapy (45 Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R0 < 40% and useful if the R0 > 70% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440.Results: Twenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p = 0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p = 0.009).Conclusion: The results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer. [ABSTRACT FROM AUTHOR]

Aims The diagnosis of primary myelofibrosis (PMF) strongly relies on the bone marrow biopsy findings, but a report model has not been standardised. Our aim was to establish general recommendations for bone marrow evaluation and standardised reporting in a case suspicious of PMF. Methods The Delphi method was employed to obtain expert consensus. An advisory panel of 10 leading members identifies a total of 37 haematopathology experts to participate. The first Delphi round included a questionnaire with three main groups of items: minimal clinical and laboratory data considered necessary before reporting, minimal descriptive aspects to record and main histological differential diagnosis. The final report content was based on consensus obtained after the second Delphi round. Results The minimal data considered necessary were age, splenomegaly, haemoglobin, leucocyte and platelet counts, differential blood cell count, leucoerythroblastic blood picture, lactate dehydrogenase (LDH) level, BCRABL and JAK2 mutational status, reticulin stain and the internal control for the reticulin staining. The minimal descriptive aspects to report were cellularity, osteosclerosis, megakaryocytic morphology and localisation, dense megakaryocytic clusters, quantity of granulocytic precursors, grade of myelofibrosis in a scale of 4, and a proposed final diagnostic approach. The entities to be considered for differential diagnosis were mainly the other classical chronic myeloproliferative neoplasms. Conclusions The Delphi method is a robust tool to determine essential information to be included in a pathology report. A standardised good-quality histopathological report form may help to homogenise PMF diagnosis. A close collaboration between the pathologist and the haematologist is desirable according to our survey. [ABSTRACT FROM AUTHOR]

Abstract: Information Retrieval systems normally have to work with rather heterogeneous sources, such as Web sites or documents from Optical Character Recognition tools. The correct conversion of these sources into flat text files is not a trivial task since noise may easily be introduced as a result of spelling or typeset errors. Interestingly, this is not a great drawback when the size of the corpus is sufficiently large, since redundancy helps to overcome noise problems. However, noise becomes a serious problem in restricted-domain Information Retrieval specially when the corpus is small and has little or no redundancy. This paper devises an approach which adds noise-tolerance to Information Retrieval systems. A set of experiments carried out in the agricultural domain proves the effectiveness of the approach presented. [Copyright &y& Elsevier]

Background & Aims: A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis., Methods: Real-world prospective study including a large dataset of MASLD patients with paired VCTE and liver biopsy from 6 centers. A total of n=1196 patients were recruited and divided in training (3 centers, Spain), internal validation (2 centers, Spain), and external validation (1 center, United States) cohorts. In patients with indeterminate liver stiffness measurements (LSM:8-12 kPa), a diagnostic algorithm was developed to identify significant fibrosis, defined as histological stage ≥F2. Statistical analysis was performed using gaussian mixture model (GMM) and k-means unsupervised clusterization., Results: From the eligible population, 33%, 29%, and 31% had indeterminate VCTE in the training, internal and external validation samples, respectively. Controlled attenuation parameter (CAP) allowed the differentiation of GMM clusters with a cut-off of 280 dB/m (AUC:0.89 [95%CI:0.86-0.97]). Within patients with <280 dB/m, a LSM between 8.0-9.0 kPa showed a 93% sensitivity and a 91% negative predictive value to exclude significant fibrosis. Among patients with ≥280 dB/m, a LSM between 10.3-12.0 kPa diagnosed significant fibrosis with a 91% specificity. Applying this algorithm to the validation cohorts, 36% of the indeterminate VCTE were re-allocated. The re-allocated high-risk group showed a prevalence of 86% significant fibrosis, opening the therapeutic window for MASLD patients., Conclusion: To identify candidates for MASLD treatment among indeterminate VCTE, an algorithm-based on the sequential combination of LSM and CAP thresholds can optimize the diagnosis of moderate-to-advanced fibrosis., (Copyright © 2024. Published by Elsevier Inc.)

In this article, we present CuentosIE (TalesEI: chatbot of tales with a message to develop Emotional Intelligence), an educational chatbot on emotions that also provides teachers and psychologists with a tool to monitor their students/patients through indicators and data compiled by CuentosIE. The use of "tales with a message" is justified by their simplicity and easy understanding, thanks to their moral or associated metaphors. The main contributions of CuentosIE are the selection, collection, and classification of a set of highly specialized tales, as well as the provision of tools (searching, reading comprehension, chatting, recommending, and classifying) that are useful for both educating users about emotions and monitoring their emotional development. The preliminary evaluation of the tool has obtained encouraging results, which provides an affirmative answer to the question posed in the title of the article., Competing Interests: The authors declare there are no competing interests., (©2024 Ferrández et al.)

Objective: To assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases., Method: A prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated., Results: In total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis ( p <0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits ( p <0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD., Conclusion: Pancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD., Competing Interests: AJ-P is employee of Quibim SL. AA-B is CEO and shareholder of Quibim SL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marti-Aguado, Ten-Esteve, Baracaldo-Silva, Crespo, Coello, Merino-Murgui, Fernandez-Paton, Alfaro-Cervello, Sánchez-Martín, Bauza, Jimenez-Pastor, Perez-Girbes, Benlloch, Pérez-Rojas, Puglia, Ferrández, Aguilera, Latorre, Monton, Escudero-García, Bosch-Roig, Alberich-Bayarri and Marti-Bonmati.)

Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant soft tissue tumor of unpredictable clinical behavior. The morphological spectrum of EMC based on histology alone can be difficult. There is no precise immunohistochemical (IHC) profile that together with the clinical parameters is able to predict the clinical outcome. We studied 31 cases confirmed as EMC. Clinical and follow-up data were recorded. Histopathological, molecular, and IHC studies were performed. Association among histopathological parameters was assessed using a chi-square test to determine homogeneity or linear trend for ordinal variables. The Kaplan-Meier proportional risk test (log rank) was used to study the impact of the histological, IHC, and molecular factors on progression-free survival (PFS) and disease-specific survival (DSS). Most EMCs showed a typical architectural pattern. Only a few cases presented an atypical histology (higher cellularity and solid pattern). IHC positivity (focal or diffuse) was present for CDK4 (100%), STAT-6 (90%), CD117 (84%), HNK-1 (81%), SATB2 (68%), and S-100 (58%). Synaptophysin and INSM1 were expressed in 22.6% and 38.7% of cases respectively. The EWSR1::NR4A3 rearrangement was found in 19 cases and 7 tumors presented the TAF15::NR4A3 fusion. Positive surgical margins together with atypical histology and expression of p53 and Ki67 correlated with worse clinical prognosis. EMCs express several IHC markers which are also seen in other soft tissue sarcomas. The molecular detection of NR4A3 rearrangement supports the differential diagnosis. Positive surgical margins together with atypical histology and positive expression of p53 and Ki-67 seem to predict a poor clinical outcome with worse prognosis, increased rate of recurrence, metastasis, and poor overall survival., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction and Objectives: Although pathology is one of the cornerstone subjects of the medical curriculum, for many students it can prove too theoretical and remote from clinical relevance. We present the results of a new distance learning project designed to make the teaching of pathology more practical and render the subject more attractive to the medical student., Materials and Methods: We developed a teaching programme which included digital pathology images and video tutorials of clinical cases; the students were required to arrive at a final diagnosis. An explanatory video of how biopsies are processed was also included. Twitter was used for rapid interaction with the students. A questionnaire was then completed by the participants evaluating the various aspects of the project., Results: All the students reached a correct diagnosis for the clinical cases. 89% of the participants were extremely satisfied with the project. The majority agreed that the different activities were interesting and useful for improving their understanding of pathology and thus recommended that they should be continued., Conclusions: Our results support the inclusion of digital pathology into the curriculum together with video tutorials to enhance undergraduate pathology teaching. In the future, such distance learning could prove a useful resource in combination with conventional face-to-face lectures and tutorials., (Copyright © 2021 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background Standardized manual region of interest (ROI) sampling strategies for hepatic MRI steatosis and iron quantification are time consuming, with variable results. Purpose To evaluate the performance of automatic MRI whole-liver segmentation (WLS) for proton density fat fraction (PDFF) and iron estimation (transverse relaxometry [R2*]) versus manual ROI, with liver biopsy as the reference standard. Materials and Methods This prospective, cross-sectional, multicenter study recruited participants with chronic liver disease who underwent liver biopsy and chemical shift-encoded 3.0-T MRI between January 2017 and January 2021. Biopsy evaluation included histologic grading and digital pathology. MRI liver sampling strategies included manual ROI (two observers) and automatic whole-liver (deep learning algorithm) segmentation for PDFF- and R2*-derived measurements. Agreements between segmentation methods were measured using intraclass correlation coefficients (ICCs), and biases were evaluated using Bland-Altman analyses. Linear regression analyses were performed to determine the correlation between measurements and digital pathology. Results A total of 165 participants were included (mean age ± standard deviation, 55 years ± 12; 96 women; 101 of 165 participants [61%] with nonalcoholic fatty liver disease). Agreements between mean measurements were excellent, with ICCs of 0.98 for both PDFF and R2*. The median bias was 0.5% (interquartile range, -0.4% to 1.2%) for PDFF and 2.7 sec -1 (interquartile range, 0.2-5.3 sec -1 ) for R2* (P < .001 for both). Margins of error were lower for WLS than ROI-derived parameters (-0.03% for PDFF and -0.3 sec -1 for R2*). ROI and WLS showed similar performance for steatosis (ROI AUC, 0.96; WLS AUC, 0.97; P = .53) and iron overload (ROI AUC, 0.85; WLS AUC, 0.83; P = .09). Correlations with digital pathology were high ( P < .001) between the fat ratio and PDFF (ROI r = 0.89; WLS r = 0.90) and moderate ( P < .001) between the iron ratio and R2* (ROI r = 0.65; WLS r = 0.64). Conclusion Proton density fat fraction and transverse relaxometry measurements derived from MRI automatic whole-liver segmentation (WLS) were accurate for steatosis and iron grading in chronic liver disease and correlated with digital pathology. Automated WLS estimations were higher, with a lower margin of error than manual region of interest estimations. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moura Cunha and Fowler in this issue.

Different fields such as linguistics, teaching, and computing have demonstrated special interest in the study of sign languages (SL). However, the processes of teaching and learning these languages turn complex since it is unusual to find people teaching these languages that are fluent in both SL and the native language of the students. The teachings from deaf individuals become unique. Nonetheless, it is important for the student to lean on supportive mechanisms while being in the process of learning an SL. Bidirectional communication between deaf and hearing people through SL is a hot topic to achieve a higher level of inclusion. However, all the processes that convey teaching and learning SL turn difficult and complex since it is unusual to find SL teachers that are fluent also in the native language of the students, making it harder to provide computer teaching tools for different SL. Moreover, the main aspects that a second language learner of an SL finds difficult are phonology, non-manual components, and the use of space (the latter two are specific to SL, not to spoken languages). This proposal appears to be the first of the kind to favor the Costa Rican Sign Language (LESCO, for its Spanish acronym), as well as any other SL. Our research focus stands on reinforcing the learning process of final-user hearing people through a modular architectural design of a learning environment, relying on the concept of phonological proximity within a graphical tool with a high degree of usability. The aim of incorporating phonological proximity is to assist individuals in learning signs with similar handshapes. This architecture separates the logic and processing aspects from those associated with the access and generation of data, which makes it portable to other SL in the future. The methodology used consisted of defining 26 phonological parameters (13 for each hand), thus characterizing each sign appropriately. Then, a similarity formula was applied to compare each pair of signs. With these pre-calculations, the tool displays each sign and its top ten most similar signs. A SUS usability test and an open qualitative question were applied, as well as a numerical evaluation to a group of learners, to validate the proposal. In order to reach our research aims, we have analyzed previous work on proposals for teaching tools meant for the student to practice SL, as well as previous work on the importance of phonological proximity in this teaching process. This previous work justifies the necessity of our proposal, whose benefits have been proved through the experimentation conducted by different users on the usability and usefulness of the tool. To meet these needs, homonymous words (signs with the same starting handshape) and paronyms (signs with highly similar handshape), have been included to explore their impact on learning. It allows the possibility to apply the same perspective of our existing line of research to other SL in the future., Competing Interests: The authors declare that they have no competing interests., (© 2021 Naranjo-Zeledón et al.)

Introduction: Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting., Methods: This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive data about patient's characteristics, neoadjuvant treatments, toxicities, curative resections, postoperative complications, pathology reports and adjuvant treatment were collected. Overall survival (OS) and progression-free survival was calculated with Kaplan-Meier method and log-rank test., Results: Between August 2011 and July 2019, 49 patients fulfilled the inclusion criteria, and all of them received neoadjuvant ChT. Fluorouracil+folinic acid, irinotecan and oxaliplatin was the most frequently used scheme (77%). The most prevalent grade 3 or 4 toxicities were neutropenia (26.5%), neurotoxicity (12.2%), diarrhoea (8.2%) and nausea (8.2%). 18 patients (36.7%) received ChRT thereafter. In total, 22 patients (44,9%) became potentially resectable and 19 of them had an R0 or R1 pancreatic resection. One was found to be unresectable at surgery and two refused surgery. A vascular resection was required in 7 (35%). No postoperative deaths were observed. Postoperative ChT was given to 12 (66.7%) of resected patients. Median OS of the whole cohort was 24,9 months (95% CI 14.1 to 35.7), with 30.6 months for resected and 13.1 months for non-resected patients, respectively (p<0.001)., Conclusion: A neoadjuvant approach in BRPC and LAUPC was well tolerated and allowed a curative resection in 38.8% of them with a potential improvement on OS., Competing Interests: Competing interests: AC declares institutional research funding from Genentech, Merck Serono, BMS, MSD, Roche,Beigene, Bayer, Servier, Lilly, Novartis, Takeda, Astellas, Natera and Fibrogen and advisory board orspeaker fees from Merck Serono, Roche, Servier, Takeda, Natera and Astellas in the last 5 years. All remaining authors have declared no conflict of interest. LS has participated in the development of teaching resources, advisory and educational programs for Abbott, Mylan, Johnson and Johnson, Medtronic, Baxter and Prim., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

At the histological level, tumor budding in colon cancer is the result of cells undergoing at least partial epithelial-to-mesenchymal transition. The microRNA 200 family is an important epigenetic driver of this process, mainly by downregulating zinc-finger E-box binding homeobox (ZEB) and transforming growth factor beta (TGF-β) expression. We retrospectively explored the expression of the miR200 family, and ZEB1 and ZEB2, and their relationship with immune resistance mediated through PD-L1 overexpression. For this purpose, we analyzed a series of 125 colon cancer cases and took samples from two different tumor sites: the area of tumor budding at the invasive front and from the tumor center. We found significant ZEB overexpression and a reduction in miR200 in budding areas, a profile compatible with epithelial-to-mesenchymal transition. In multivariate analysis of the cases with localized disease, low miR200c expression in budding areas, but not at the tumor center, was an adverse tumor-specific survival factor (hazard ratio: 0.12; 95% confidence interval: 0.03-0.81; p = 0.02) independent of the clinical stage of the disease. PD-L1 was significantly overexpressed in the budding areas and its levels correlated with a mesenchymal transition profile. These results highlight the importance of including budding areas among the samples used for biomarker evaluation and provides relevant data on the influence of mesenchymal transition in the immune resistance mediated by PD-L1 overexpression.

Background and Objective: Clinical management of adenocarcinoma of the pancreas is complex, and requires a multidisciplinary approach. The same applies for the premalignant lesions that are increasingly being diagnosed. The current document is an update on the diagnosis and management of premalignant lesions and adenocarcinoma of the pancreas., Patients and Methods: A conference to establish the basis of the literature review and manuscript redaction was organized by the Grupo Español Multidisciplinar en Cáncer Digestivo. Experts in the field from different specialties (Gastroenterology, Surgery, Radiology, Pathology, Medical Oncology and Radiation Oncology) met to prepare the present document., Results: The current literature was reviewed and discussed, with subsequent deliberation on the evidence., Conclusions: Final recommendations were established in view of all the above., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Introduction: Involvement of surgical resection margins is a fundamental prognostic factor in pancreatic oncological surgery. However, there is a lack of standardized histopathology definition. The aims of this study are to investigate the real rate of R1 resections when surgical specimens are evaluated according to a standardized protocol and to study its survival implications., Patients Y Methods: One hundred consecutive surgically resected patients with pancreatic ductal adenocarcinoma were included in the study. They were further divided in 2 groups: pre-protocol, evaluated before the introduction of the standardized protocol and post-protocol, analyzed with the standardized protocol., Results: R0 resection rate in the pre-protocol group was 78%, falling to 47% after the introduction of the standardized protocol (p=0,003). The posterior retroperitoneal margin was the most frequently involved margin. In cases with tumors located at the pancreatic head and analyzed according to the standardized protocol R1 involvement negatively affected survival. Median survival in the R0 group was 22 months versus 16 in those with the margin involved (HR: 2.044; IC 95% 1,00-4,16; P=.043)., Conclusions: Standardized evaluation of the retroperitoneal margins in pancreatic cancer increases the rate of R1 patients. In cases with pancreatic cancer located at the pancreatic head involvement of posterior retroperitoneal margin significantly decreases survival., (Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.)

Purpose: To identify quality indicators and establish acceptable quality limits (AQLs) in pancreatic oncologic surgery using a formal statistical methodology., Methods: Indicators have been identified through systematic literature reviews and guidelines for pancreatic surgery. AQLs were determined for each indicator with confidence intervals of 99.8 and 95 % above and below the weighted average by sample size from the different series examined., Results: Several indicators have been identified with the following results as AQLs: resectability rate >59 %; morbidity, mortality, and pancreatic fistula rate in pancreaticoduodenectomy <55, <5, and <16 %, respectively; morbidity, mortality, and fistula rate in distal pancreatectomy <53, <4, and <31 %, respectively; number of lymph nodes retrieved >15; R1 resection <46 %; survival at 1, 3, and 5 years >54, >19, and >8 %, respectively., Conclusions: A series of different indicators for quality surgical care outcome in pancreatic cancer, as well as their limits, have been determined according to a standard methodology.

Among the different processes occurring during the evolution of liver disease, fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant irrespective of the underlying etiology. Cirrhosis is the end-stage of this reaction. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. The aim of this study was to demonstrate the applicability of 1H high resolution magic angle spinning (HR-MAS) NMR spectroscopy in the biochemical profile determination of human liver needle biopsy samples for the characterization of metabolic alterations related to the severity of liver disease. We recorded and analyzed HR-MAS spectra of 68 liver tissue samples obtained by needle biopsy from patients with chronic liver disease. Multivariate analysis was applied to these data to obtain discrimination patterns and to reveal relevant metabolites. The metabolic characterization of liver tissue from needle biopsies by HR-MAS NMR spectroscopy provided differential patterns for cirrhotic and non-cirrhotic chronic liver disease tissue. Metabolites closely related to the liver metabolism such as some fatty acids, glucose and amino acids show differences between the two groups. Phospholipid precursors, which have been previously correlated with hepatic lesions also show differences. Furthermore, the correlation between histologically assessed liver disease stages and the levels of the most discriminative metabolites show that liver dysfunction is present at the initial stages of chronic hepatic lesions. Overall, this work suggests that the additional information obtained by NMR metabolomics applied to needle biopsies of human liver may be useful for assessing metabolic alterations and liver dysfunction in chronic liver disease.

High-resolution magic angle spinning (HR-MAS) 1H NMR spectroscopy of intact human liver needle biopsies has not been previously reported. HR-MAS NMR spectra collected on 17 specimens with tissue amounts between approximately 0.5 and 12 mg showed very good spectral resolution and signal-to-noise ratios. One-dimensional 1H spectra revealed many intense signals corresponding to cellular metabolites. In addition, some high molecular weight metabolites, such as glycogen and mobile fatty acids, could be observed in some spectra. Resonance assignments for 22 metabolites were obtained by combining the analysis of three different types of 1D 1H spectral editing, such as T2 filtering or the nuclear Overhauser effect and 2D TOCSY and 13C-HSQC spectra. Biochemical stability of the liver tissue during up to 16 h of magic angle spinning at 277 K was studied. Biochemical trends corresponding to the different pathologies were observed, involving free fragments of lipids among other metabolites. NMR signal intensity ratios can be useful for discrimination among non-pathological, hepatitis C affected and cirrhotic liver tissues. Overall, this work demonstrates the applicability of HR-MAS NMR spectroscopy to the biochemical characterization of needle biopsies of the human liver., (2006 John Wiley & Sons, Ltd.)