Clinical impact and prognostic role of KRAS/BRAF/PIK3CA mutations in stage I colorectal cancer

Stage I colorectal carcinoma has excellent prognosis, with 5-year survival rate up to 95%. The occurrence of lymphovascular invasion, tumor budding, high number of PDC, or lymph node micrometastases is associated with tumor progression. The aim of this study was to evaluate the mutational status of 62 stage I colorectal carcinomas (CRC) (taken from 37 patients surviving more than five years since the initial diagnosis and from 25 patients who died of disease) and to correlate it with histopathological features and the clinical outcome. Mutations of KRAS, NRAS, BRAF, and PIK3CA genes were analyzed through Myriapod Colon Status Kit, using the high-throughput genotyping platform Sequenom MassARRAY System. Mutations in those genes were found in 31 cases (50%) and mainly in those with poor prognosis. The most frequent mutations occurred at codons 12 and 13 of the KRAS gene (40% of cases). We found concomitant PIK3CA mutations in 5 cases (8%). The presence of PIK3CA mutations was mainly observed in tumors with poor prognosis and with unfavorable histopathological prognostic features. High PDC grade (P = 0 0112), the presence of tumor budding (P = 0 0334), LVI (P < 0 0001), KRAS mutations (P = 0 0228), PIK3CA mutations (P = 0 0214), multiple genetic mutations in KRAS and PIK3CA genes (P = 0 039), and nodal micrometastases (P < 0 0001) were significant prognostic variables for CSS. The presence of LVI was the only independent and statistically significant prognostic variable for CSS in our cohort of pTNM stage I CRCs. The analysis of KRAS/PIK3CA mutational status may be used to identify patients with stage I CRC at high risk of bad outcome and who may need additional treatments, including biological therapies

Global attractors for Cahn-Hilliard equations with non constant mobility

We address, in a three-dimensional spatial setting, both the viscous and the standard Cahn-Hilliard equation with a nonconstant mobility coefficient. As it was shown in J.W. Barrett and J.W. Blowey, Math. Comp., 68 (1999), 487-517, one cannot expect uniqueness of the solution to the related initial and boundary value problems. Nevertheless, referring to J. Ball's theory of generalized semiflows, we are able to prove existence of compact quasi-invariant global attractors for the associated dynamical processes settled in the natural "finite energy" space. A key point in the proof is a careful use of the energy equality, combined with the derivation of a "local compactness" estimate for systems with supercritical nonlinearities, which may have an independent interest. Under growth restrictions on the configuration potential, we also show existence of a compact global attractor for the semiflow generated by the (weaker) solutions to the nonviscous equation characterized by a "finite entropy" condition

Natural cytotoxicity impairment in familial haemophagocytic lymphohistiocytosis.

Ten children with the characteristic clinical and haematological features of haemophagocytic lymphohistiocytosis are reported. Four patients treated with a combination of drugs comprising etoposide, methotrexate, and steroids were in complete remission after 10 to 30 months. Natural cytotoxic mechanisms including natural killer cell activity, antibody dependent cell mediated cytotoxicity, lymphokine activated killer cell activity, and natural killer cell like activity were persistently absent or severely impaired in these four patients despite their clinical remission. Their parents and one healthy sibling also had impaired natural cytotoxic mechanisms. Constitutional impairment of natural cytotoxic mechanisms could be important in the pathogenesis of haemophagocytic lymphohistiocytosis

Critical structure factor in Ising systems

We perform a large-scale Monte Carlo simulation of the three-dimensional Ising model on simple cubic lattices of size L^3 with L=128 and 256. We determine the corresponding structure factor (Fourier transform of the two-point function) and compare it with several approximations and with experimental results. We also compute the turbidity as a function of the momentum of the incoming radiation, focusing in particular on the deviations from the Ornstein-Zernicke expression of Puglielli and Ford.Comment: 16 page

Auditory sensory memory and working memory skills : Association between frontal MMN and performance scores

Objective: Memory is the faculty responsible for encoding, storing and retrieving information, comprising several sub-systems such as sensory memory (SM) and working memory (WM). Some previous studies exclusively using clinical population revealed associations between these two memory systems. Here we aimed at investigating the relation between modality-general WM performance and auditory SM formation indexed by magnetic mismatch negativity (MMN) responses in a healthy population of young adults. Methods: Using magnetoencephalography (MEG), we recorded MMN amplitudes to changes related to six acoustic features (pitch, timbre, location, intensity, slide, and rhythm) inserted in a 4-tone sequence in 86 adult participants who were watching a silent movie. After the MEG recordings, participants were administered the WM primary subtests (Spatial Span and Letter Number Sequencing) of Wechsler Memory Scale (WMS). Results: We found significant correlations between frontal MMN amplitudes to intensity and slide deviants and WM performance. In case of intensity, the relation was revealed in all participants, while for slide only in individuals with a musical background. Conclusions: Automatic neural responses to auditory feature changes are increased in individuals with higher visual WM performance. Significance: Conscious WM abilities might be linked to pre-attentive sensory-specific neural skills of prediction and short-term storage of environmental regularities. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Colon cancer in a 12-year-old girl with hypertriglyceridemia

Colorectal cancer is usually considered a disease of the elderly; however, in a small fraction of patients (2%-3% of all affected individuals), colorectal malignancies may develop earlier. The reasons whereby some individuals develop colorectal cancer at a young age are poorly understood. In a 12-year-old girl, a malignancy was diagnosed in the ascending colon. There was no familial history of Lynch syndrome or familial adenomatous polyposis. The metabolic profile of the patient revealed hypertriglyceridemia and low high-density lipoprotein cholesterol levels at nine years, then diagnosed as familial hypertriglyceridemia due to a constitutional mutation in the APOA5 gene (c.427delC). Moreover, variants possibly increasing the risk of cancer were detected in MSH6 (c.3438+11_3438+14delCTTA, intron 5) and APC (I1307K). The patient showed a rather unusual dietary pattern, since her basic alimentation from weaning consisted almost exclusively of meat homogenates and, subsequently, roasted meat or cutlets. Other foods, including fish, vegetables, sweets, and pasta, were refused. In this case, genetic and environmental factors could have acted in a particularly accelerated manner. Indeed, the genetic background of the patient (familial hypertriglyceridemia and polymorphisms predisposing to colorectal cancer) may have favored a dietary-driven colorectal carcinogenesis, resulting in an extremely early onset development of malignancy

Poorly differentiated clusters (PDC) in colorectal cancer: Does their localization in tumor matter?

Poorly differentiated clusters (PDC) are aggregates of at least five neoplastic cells lacking evidence of glandular differentiation. By definition, they can be present at the invasive front (peripheral PDC or pPDC) and within the tumor stroma (central PDC or cPDC). In colorectal cancer (CRC), PDC are considered adverse prognosticators and seem to reflect epithelial mesenchymal transition (EMT). In this study, we have investigated the immuno-expression of two EMT-related proteins, E-cadherin and β-catenin, in PDC of primary CRCs and matched liver metastases. pPDC always showed nuclear β-catenin staining and diffusely reduced/absence of E-cadherin expression as opposed cPDC which showed nuclear β-catenin immunoreactivity and E-cadherin expression in about 50% of cases. In addition, the pattern of β-catenin and E-cadherin expression differed between PDC and the main tumor, and between primary CRC and liver metastasis (LM), in a percentage of cases. A discordant pattern of β-catenin and E-cadherin expression between pPDC and cPDC, between main tumor and cPDC, and between primary CRC and LM, confirms that EMT is a dynamic and reversible process in CRC. On the overall, this suggests that pPDC and cPDC are biologically different. We may advocate that PDC develop at the tumor center (cPDC) and then some of them migrate towards the tumor periphery while progressively completing EMT process (pPDC). Based on these results, PDC presence and counting may have different prognostic relevance if the assessment is done at the invasive front of the tumor or in the intratumor stroma

Outcomes in Hybrid Breast Reconstruction: A Systematic Review

Background and Objectives: Lipofilling is a commonly performed procedure worldwide for breast augmentation and correction of breast contour deformities. In breast reconstruction, fat grafting has been used as a single reconstructive technique, as well as in combination with other procedures. The aim of the present study is to systematically review available studies in the literature describing the combination of implant-based breast reconstruction and fat grafting, focusing on safety, complications rate, surgical sessions needed to reach a satisfying reconstruction, and patient-reported outcomes. Materials and Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) throughout the whole review protocol. A systematic review of the literature up to April 2022 was performed using Medline, Embase, and Cochrane Library databases. Only studies dealing with implant-based breast reconstruction combined with fat grafting were included. Results: We screened 292 articles by title and abstract. Only 48 articles were assessed for full-text eligibility, and among those, 12 studies were eventually selected. We included a total of 753 breast reconstructions in 585 patients undergoing mastectomy or demolitive breast surgeries other than mastectomy (quadrantectomy, segmentectomy, or lumpectomy) due to breast cancer or genetic predisposition to breast cancer. Overall, the number of complications was 60 (7.9%). The mean volume of fat grafting per breast per session ranged from 59 to 313 mL. The mean number of lipofilling sessions per breast ranged from 1.3 to 3.2. Conclusions: Hybrid breast reconstruction shows similar short-term complications to standard implant-based reconstruction but with the potential to significantly decrease the risk of long-term complications. Moreover, patient satisfaction was achieved with a reasonably low number of lipofilling sessions (1.7 on average)