A coordinate deregulation of microRNAs expressed in mucosa adjacent to tumor predicts relapse after resection in localized colon cancer

Up to 20% of colorectal cancer (CRC) node-negative patients develop loco-regional or distant recurrences within 5 years from surgery. No predictive biomarker able to identify the node-negative subjects at high risk of relapse after curative treatment is presently available.Forty-eight localized (i.e. stage I-II) colon cancer patients who underwent radical tumor resection were considered. The expression of five miRNAs, involved in CRC progression, was investigated by qRT-PCR in both tumor tissue and matched normal colon mucosa.Interestingly, we found that the coordinate deregulation of four miRNAs (i.e. miR-18a, miR-21, miR-182 and miR-183), evaluated in the normal mucosa adjacent to tumor, is predictive of relapse within 55 months from curative surgery.Our results, if confirmed in independent studies, may help to identify high-risk patients who could benefit most from adjuvant therapy. Moreover, this work highlights the importance of extending the search for tissue biomarkers also to the tumor-adjacent mucosa

A new multianodic large area photomultiplier to be used in underwater neutrino detectors

In this article we describe the properties of a new 10-in. hemispherical photomultiplier manufactured by Hamamatsu. The prototype has a segmented photocathode and four independent amplification stages. The photomultiplier is one of the main components of a newly designed direction-sensitive optical module to be employed in large-scale underwater neutrino telescopes. The R&D activity has been co-funded by the INFN and the KM3NeT Consortium. The prototype performance fully meets with the design specifications

Delphi initiative for early-onset colorectal cancer (DIRECt). International Management Guidelines.

BACKGROUND AND AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), comprised of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was employed to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. Based on current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors.The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC

High Risk of Rectal Cancer and of Metachronous Colorectal Cancer in Probands of Families Fulfilling the Amsterdam Criteria.

Abstract OBJECTIVE: To investigate the risk of metachronous colorectal cancer (CRC), its impact on survival, and the risk of rectal cancer in a cohort of probands meeting the Amsterdam criteria. BACKGROUND: Several determinants of decision-making for the management of CRC in patients with a putative diagnosis of Lynch syndrome are scarcely defined, and many of them undergo segmental bowel resection instead of the advised total colectomy. METHODS: A retrospective cohort study was conducted on 65 probands of the Amsterdam-positive families who had surgery for primary CRC and at least 5-year surveillance thereafter. The rates of metachronous CRC and of rectal cancer were evaluated, together with their association with preoperatively available clinical predictors. Differences in overall survival between patients with and without metachronous CRC were evaluated using a time-dependent Cox model. RESULTS: Seventeen patients (26.2%) had metachronous CRC. No clinical feature was associated with an increased risk of its development. The risk of death in patients with metachronous CRC was 6-fold increased. Neither a 2-year interval endoscopic surveillance after surgery, nor total colectomy was associated with a significant reduction in metachronous CRC. Eighteen patients (23.7%) had rectal cancer at first presentation, 5 patients of the remainder (10.6%) developed rectal cancer after primary colon resection. Two patients undergoing total colectomy developed a metachronous rectal cancer (18.2%). A first-degree family history of rectal cancer was associated with an increased risk of rectal cancer. CONCLUSIONS: Probands of families fulfilling the Amsterdam criteria carry a high risk of rectal cancer and of metachronous CRC. Total proctocolectomy, or total colectomy and a 1-year interval of proctoscopic surveillance should be advised when a high risk of rectal cancer can be predicted

Programmed cell death-ligand 1 (PD-L1) overexpression in ampulla of Vater carcinoma and its pre-invasive lesions

PD-1/PD-L1 checkpoint immunotherapy has recently been proposed as a promising treatment in relapsed/refractory disease, eventually used in combination with the traditional chemotherapy in different cancer settings. No data are still now available about PD-L1 expression in ampulla of Vater carcinoma and its preinvasive lesions

Overview of the RFX-mod contribution to the international Fusion Science Program

The RFX-mod device is operated both as a reversed field pinch (RFP), where advanced regimes featuring helical shape develop, and as a tokamak. Due to its flexibility, RFX-mod is contributing to the solution of key issues in the roadmap to ITER and DEMO, including MHD instability control, internal transport barriers, edge transport and turbulence, isotopic effect, high density limit and three-dimensional (3D) non-linear MHD modelling. This paper reports recent advancements in the understanding of the self-organized helical states, featuring a strong electron transport barrier, in the RFP configuration; the physical mechanism driving the residual transport at the barrier has been investigated. Following the first experiments with deuterium as the filling gas, new results concerning the isotope effect in the RFP are discussed. Studies on the high density limit show that in the RFP it is related to a toroidal particle accumulation due to the onset of a convective cell. In the tokamak configuration, q(a) regimes down to q(a) = 1.2 have been pioneered, with (2,1) tearing mode (TM) mitigated and (2,1) resistive wall mode (RWM) stabilized: the control of such modes can be obtained both by poloidal and radial sensors. Progress has been made in the avoidance of disruptions due to the (2,1) TM by applying q(a) control, and on the general issue of error field control. The effect of externally applied 3D fields on plasma flow and edge turbulence, sawtooth control and runaway electron decorrelation has been analysed. The experimental program is supported by substantial theoretical activity: 3D non-linear visco-resistive MHD and non-local transport modelling have been advanced; RWMs have been studied by a toroidal MHD kinetic hybrid stability code

Recent achievements of the NEMO project

The status of the activities towards the realization of a km3 Cherenkov neutrino detector carried out by the NEMO Collaboration is described. The realization of a Phase-1 project, which is under way, will validate the proposed technologies for the realization of the km3 detector on a Test Site at 2000 m depth. The realization of a new infrastructure on the candidate site (Phase-2 project) will provide the possibility to test detector components at 3500 m depth

KM3NeT: Technical design report.

KM3NeT is a deep‐sea multidisciplinary observatory in the Mediterranean Sea that will provide innovative science opportunities spanning Astroparticle Physics and Earth and Sea Science. This is possible through the synergy created by the use of a common infrastructure allowing for long term continuous operation of a neutrino telescope and marine instrumentation. The present KM3NeT Design Study concludes with this Technical Design Report which develops the ideas put forward in the Conceptual Design Report published in April 2008