...they proposed a new grading system including both WHO grade and microsatellite instability (MSI) status for CRC and showed that this grading has higher predictive value for worse survival compared ...with WHO grading alone 1. ...PDC grade may better reflect the biologic aggressiveness of CRC compared with WHO grading, and its use may have higher prognostic significance regardless of the biomolecular profile of CRC.
Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer-related deaths in Western industrialized countries. Lifetime risk of colorectal cancer ...may reach 6% of the population living in developed countries. In the current era of personalized medicine, CRC is no longer considered as a single entity. In more recent years many studies have described the distinct differences in epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and outcome depending on the anatomical site. The aim of our study is to assess in a multidimensional model the association between metabolic status and inflammatory and autophagic changes in the normal colorectal mucosa classified as right-sided, left-sided and rectum, and the presence of adenomas. One hundred and sixteen patients undergoing colonoscopy were recruited and underwent a complete serum lipid profile, immunofluorescence analysis of colonic biopsies for MAPLC3 and myeloperoxidase expression, matched with clinical and anthropometric characteristics. Presence of adenomas correlated with cholesterol (total and LDL) levels, IL-6 levels, and MAPLC3 tissue expression, especially in the right colon. In conclusion, serum IL-6 amount and autophagic markers could be good predictors of the presence of colorectal adenomas.
New lymphatic structures in colon cancer Manenti, Antonio, M.D; Pavesi, Erica, M.D; Farinetti, Alberto, M.D ...
The American journal of surgery,
05/2016, Letnik:
211, Številka:
5
Journal Article
Recenzirano
Considering all these features these neo-generated organs deserve to be considered tertiary lymphatic structures.2,3 This process, observed independently from the presence of LN metastases, can be ...associated with intratumoral lymphocytic infiltration and it is generally considered as a tissue immune response to persistent antigenic stimuli.2-4 A corresponding neogenesis of lymphatic structures was observed in other cancers (breast, lung, skin melanoma, and so forth), and with minor number, also in inflammatory diseases of the colon.2 In our experience, based on histological examinations of surgical specimens, this immunological activity was demonstrated only in the regional lymphatic district. Because of its complexity, this topic requires further research; maybe tomorrow this colon cancer feature will be considered among the prognostic signs.5
Intrahepatic cholangiocarcinoma (iCCA) is an anatomically and biologically distinct entity with a rising incidence and a poor prognosis on conventional treatments. Surgery followed by adjuvant ...chemotherapy is a potentially curative option in resectable cases, while palliative-intent chemotherapy is the standard-of-care in the advanced setting. Technological advances through massive parallel sequencing have enabled a deeper understanding of disease biology with the identification of several draggable molecular vulnerabilities in nearly 50% of cases. Among them, gene fusions involving the fibroblast growth factor receptor 2 (FGFR2) are the most therapeutically exploited so far with a number of Phase II clinical trials investigating FGFR2 inhibitors showing unprecedented efficacy results in this molecular subgroup. Over the last year, these efforts have culminated in the US FDA-approval of pemigatinib and infigratinib, the first two oral selective FGFR2 targeted agents for previously treated, locally advanced or metastatic iCCA driven by FGFR2 fusion or rearrangements. While first-line Phase III trials are currently underway to test these targeted approach against standard-of-care chemotherapy, translational studies are trying to better understand primary and secondary resistance mechanisms in order to optimize FGFR2 blockade in iCCA. In this article, we extensively reviewed the current evidence on the biological rationale, as well as preclinical and clinical development of FGFR inhibitors in iCCA. Keywords: biliary cancer, cholangiocarcinoma, intrahepatic, FGFR2, targeted therapy, precision medicine
Relatively little is known on the genotype-phenotype correlations between
SMAD4
gene mutations, juvenile polyposis of the intestine and Hereditary Hemorrhagic Teleangectasia. We describe a family in ...which the proband (a 46-year old woman) had massive polyposis of the stomach—leading to surgery—with high-grade dysplasia at histology. Molecular analysis was carried out using Next Generation sequencing techniques with Miseq Illumina Platforms and a minimal coverage of 40 reads. In the proband, the analysis showed the presence of a truncating mutation in the
SMAD4
gene (c.1213dupC, a variant previously associated with juvenile polyposis and Hereditary Hemorrhagic Teleangectasia). The same mutation was detected in two other members of the family (father and brother of the proband), who showed massive polypoid involvement of the stomach at gastroscopy. By taking the family history, subtle evidence of Hereditary Teleangectasia was found (nasal bleeding and arterovenous malformations) in the three gene carriers. Colonoscopy showed polyp occurrence in all three affected members with
SMAD4
mutation, with prevalence of adenomatous lesions in one (father), of hamartomas in the brother, and of a mix of histological types in the proband. The main features of the family can be summarized as follows: (A) In hereditary juvenile polyposis, lesions of different histology can be detected at colonoscopy; (B) In the gene carriers of
SMAD4
mutations, lesions of the stomach require careful surveillance and, when necessary, surgical interventions; (C) Signs and symptoms of Hereditary Hemorrhagic Teleangectasia should be suspected (and searched) in individuals with
SMAD4
constitutional mutations.
Device-to-device communication, as provided by the third generation partnership project standardization, can play a vital role in designing a reliable pervasive public safety network, which allows ...the user equipment (UEs) to communicate directly with each other in emergency situations. In this paper, we analyze the performance of direct discovery, one of the features introduced by proximity services. This is examined in heterogeneous environments using the OpenAirInterface open-source software and USRP hardware platform. The experimental results highlight the suitable values for different gains and frequencies of the UEs for performing reliable baseline direct discovery in out-of-coverage scenarios. We evaluate the performance of direct discovery in terms of reliability and maximum range in outdoor and indoor scenarios. Furthermore, we propose a context-aware energy-efficient heuristic algorithm for direct discovery with the aim of extending the network lifetime in emergency scenarios. This heuristic yields significant improvements in UE lifetime (20-52%) and reduces redundant transmissions of discovery messages compared to the baseline approach.
Fatalities following contrast medium exposure are extremely rare in clinical routine, though they may occur as an exception. Some may fall under the purview of the inquiring authorities and forensic ...pathologists due to their in-hospital occurrence. The purpose of this study was to assess the risk factors for anaphylaxis due to contrast medium administration that can be identified in fatal cases.
Fatalities occurred during the course of clinical investigations with contrast media described in the literature and fatal reactions to contrast agents that had undergone forensic investigations in our medicolegal center were reviewed with respect to patient characteristics, administered contrast medium, performed biochemical investigations and potential risk factors identified based on clinical history and medical records.
Biochemical investigations into the fatal cases examined in our facility revealed increased mast cell tryptase, total IgE and activated mast cells in all subjects. Data obtained from the literature and our own investigations indicated that in only a minority of the fatal cases had there been previous exposure to contrast compounds, while most cases of severe anaphylaxis involved patients who apparently reacted on initial exposure.
Most fatal cases failed to present any identifiable predisposing conditions out of those traditionally considered as risk factors for an anaphylactic reaction to contrast compounds in the medical histories of the patients. Comprehensive clinical histories and thorough reviews of medical data, along with exhaustive forensic investigations, provide information that is relevant in order to better appreciate the interwoven relationships linking all factors potentially involved in the pathogenesis of fatal anaphylaxis to contrast media.
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