Purpose
To assess the ability of radiomic features (RF) extracted from contrast-enhanced CT images (ceCT) and non-contrast-enhanced (non-ceCT) in discriminating histopathologic characteristics of ...pancreatic neuroendocrine tumors (panNET).
Methods
panNET contours were delineated on pre-surgical ceCT and non-ceCT. First- second- and higher-order RF (adjusted to eliminate redundancy) were extracted and correlated with histological panNET grade (G1 vs G2/G3), metastasis, lymph node invasion, microscopic vascular infiltration. Mann–Whitney with Bonferroni corrected
p
values assessed differences. Discriminative power of significant RF was calculated for each of the end-points. The performance of conventional-imaged-based-parameters was also compared to RF.
Results
Thirty-nine patients were included (mean age 55-years-old; 24 male). Mean diameters of the lesions were 24 × 27 mm. Sixty-nine RF were considered. Sphericity could discriminate high grade tumors (AUC = 0.79,
p
= 0.002). Tumor volume (AUC = 0.79,
p
= 0.003) and several non-ceCT and ceCT RF were able to identify microscopic vascular infiltration: voxel-alignment, neighborhood intensity-difference and intensity-size-zone families (AUC ≥ 0.75,
p
< 0.001); voxel-alignment, intensity-size-zone and co-occurrence families (AUC ≥ 0.78,
p
≤ 0.002), respectively). Non-ceCT neighborhood-intensity-difference (AUC = 0.75,
p
= 0.009) and ceCT intensity-size-zone (AUC = 0.73,
p
= 0.014) identified lymph nodal invasion; several non-ceCT and ceCT voxel-alignment family features were discriminative for metastasis (
p
< 0.01, AUC = 0.80–0.85). Conventional CT ‘necrosis’ could discriminate for microscopic vascular invasion (AUC = 0.76,
p
= 0.004) and ‘arterial vascular invasion’ for microscopic metastasis (AUC = 0.86,
p
= 0.001). No conventional-imaged-based-parameter was significantly associated with grade and lymph node invasion.
Conclusions
Radiomic features can discriminate histopathology of panNET, suggesting a role of radiomics as a non-invasive tool for tumor characterization.
Trial registration number
: NCT03967951, 30/05/2019
Review on how the IL‐17 superfamily induces de novo chemotaxis of GC B cells to CXCL12 and CXCL13 by modulating RGS16 expression.
The germinal center (GC) is a dynamic structure formed by ...proliferating B cells in the follicles of secondary lymphoid organs during T cell‐dependent antibody responses to exogenous antigens. GC is composed by a dark zone, enriched in proliferating centroblasts (CBs), and a light zone where CBs migrate and transform into centrocytes (CCs), a minority of which is selected to survive, undergoes Ig class‐switch recombination, and differentiates into memory B cells or long‐lived plasma cells. CBs express CXCR4 and are attracted to the dark zone by stromal cell‐derived CXCL12, whereas CCs express CXCR5 and are recruited to the light zone along a gradient of CXCL13 produced by follicular dendritic cells (FDCs). Therefore, CXCL12 and CXCL13 play crucial roles in the regulation of GC B cell trafficking. Among the numerous molecules involved in GC formation, IL‐17A represents a recent addition. Its involvement has been demonstrated in mouse models of human autoimmune or infectious diseases. IL‐17A belongs to the IL‐17 cytokine superfamily, together with 5 additional structurally related cytokines. We have recently demonstrated that IL‐17A renders freshly isolated tonsil GC B cells competent to migrate to CXCL12 and CXCL13 through a NF‐κBp65‐dependent mechanism. Here, we review the role of IL‐17A on GC cells and discuss, for the first time, common effects of the cognate cytokines IL‐25 and IL‐17B on GC B cell function.
Current understanding of the complex pathogenesis of COVID-19 interstitial pneumonia pathogenesis in the light of biopsies carried out in early/moderate phase and histology data obtained at ...postmortem analysis is discussed. In autopsies the most observed pattern is diffuse alveolar damage with alveolar-epithelial type-II cell hyperplasia, hyaline membranes, and frequent thromboembolic disease. However, these observations cannot explain some clinical, radiological and physiopathological features observed in SARS-CoV-2 interstitial pneumonia, including the occurrence of vascular enlargement on CT and preserved lung compliance in subjects even presenting with or developing respiratory failure. Histological investigation on early-phase pneumonia on perioperative samples and lung biopsies revealed peculiar morphological and morpho-phenotypical changes including hyper-expression of phosphorylated STAT3 and immune checkpoint molecules (PD-L1 and IDO) in alveolar-epithelial and endothelial cells. These features might explain in part these discrepancies.
Abstract Background The advent of molecular-based methods of identification and characterization of complex microbial populations has led to a new era of microbial discovery. A detailed and ...comprehensive analysis of the microbial ecosystem of the pathologic and healthy prostate tissues has not been yet reported. Objectives To characterize the microbiome possibly associated to the pathologic prostate microenvironment. Design, setting, and participants The microbiome profile of tumor, peri-tumor, and nontumor tissues was assessed on 16 radical prostatectomy-specimens. Outcome measurements and statistical analysis Microbiome analysis was assessed by massive ultradeep pyrosequencing. Bacteria load was expressed as a percentage of the total number of bacteria. The statistical significance of differences among specimen-groups was tested with Friedman's test (Dunn posthoc test) and Wilcoxon rank-sum test. Results and limitations Three phyla, six classes, nine orders, 14 families, and 11 genera were above the set threshold value of 1%, respectively. Significant differences in specific microbial populations among tumor/peri-tumor and nontumor prostate specimens were observed at certain taxonomic levels. Among genera, Propionibacterium spp. were the most abundant. Staphylococcus spp. were more represented in the tumor/peri-tumor tissues ( p < 0.05). The restricted number of specimens represents a potential limitation. Conclusions The prostate contains a plethora of bacteria, which set themselves within the gland with a distribution dependent on the nature of the tissue, thus suggesting a possible pathophysiological correlation between the composition of the local microbial niche and the presence of the tumor itself. Future studies will help to clarify the role of these specific bacteria and their potential to be exploited as new biomarkers. Patient summary The pathological prostate is populated by specific microbial populations, whose distribution varies according to the nature of the tissue. This finding opens interesting perspectives for the identification of novel therapeutic approaches and biomarkers.
Macroautophagy (autophagy) is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or ...context. Here we show that pancreatic cancers have a distinct dependence on autophagy. Pancreatic cancer primary tumors and cell lines show elevated autophagy under basal conditions. Genetic or pharmacologic inhibition of autophagy leads to increased reactive oxygen species, elevated DNA damage, and a metabolic defect leading to decreased mitochondrial oxidative phosphorylation. Together, these ultimately result in significant growth suppression of pancreatic cancer cells in vitro. Most importantly, inhibition of autophagy by genetic means or chloroquine treatment leads to robust tumor regression and prolonged survival in pancreatic cancer xenografts and genetic mouse models. These results suggest that, unlike in other cancers where autophagy inhibition may synergize with chemotherapy or targeted agents by preventing the up-regulation of autophagy as a reactive survival mechanism, autophagy is actually required for tumorigenic growth of pancreatic cancers de novo, and drugs that inactivate this process may have a unique clinical utility in treating pancreatic cancers and other malignancies with a similar dependence on autophagy. As chloroquine and its derivatives are potent inhibitors of autophagy and have been used safely in human patients for decades for a variety of purposes, these results are immediately translatable to the treatment of pancreatic cancer patients, and provide a much needed, novel vantage point of attack.
Circulating tumour cell (CTC) clusters have been proposed to be major players in the metastatic spread of breast cancer, particularly during advanced disease stages. Yet, it is unclear whether or not ...they manifest in early breast cancer, as their occurrence in patients with metastasis-free primary disease has not been thoroughly evaluated. In this study, exploiting nanostructured titanium oxide-coated slides for shear-free CTC identification, we detect clustered CTCs in the curative setting of multiple patients with early breast cancer prior to surgical treatment, highlighting their presence already at early disease stages. These results spotlight an important aspect of metastasis biology and the possibility to intervene with anti-cluster therapeutics already during the early manifestation of breast cancer.
ABSTRACT
Activating mutations in the BRAF-MAPK pathway have been reported in histiocytoses, hematological inflammatory neoplasms characterized by multi-organ dissemination of pro-inflammatory myeloid ...cells. Here, we generate a humanized mouse model of transplantation of human hematopoietic stem and progenitor cells (HSPCs) expressing the activated form of BRAF (
BRAF
V600E
). All mice transplanted with
BRAF
V600E
-expressing HSPCs succumb to bone marrow failure, displaying myeloid-restricted hematopoiesis and multi-organ dissemination of aberrant mononuclear phagocytes. At the basis of this aggressive phenotype, we uncover the engagement of a senescence program, characterized by DNA damage response activation and a senescence-associated secretory phenotype, which affects also non-mutated bystander cells. Mechanistically, we identify TNFα as a key determinant of paracrine senescence and myeloid-restricted hematopoiesis and show that its inhibition dampens inflammation, delays disease onset and rescues hematopoietic defects in bystander cells. Our work establishes that senescence in the human hematopoietic system links oncogene-activation to the systemic inflammation observed in histiocytic neoplasms.
To develop and validate a simple prognostic score to predict major postoperative complications after pancreaticoduodenectomy (PD).
PD still carries a high rate of severe postoperative complications. ...No specific score is currently available to stratify the patient's risk of major morbidity.
Between 2002 and 2010, preoperative, intraoperative, and outcome data from 700 consecutive patients undergoing PD in our institution were prospectively collected in an electronic database. Major complications were defined as levels III to V of Clavien-Dindo classification. On the basis of a multivariate regression model, the score was developed using a random two-thirds of the population (n = 469) and was validated on the remaining 231 patients.
Major complication rate was 16.7% (117/700). Significant predictors included in the scoring system were: pancreas texture, pancreatic duct diameter, operative blood loss, and ASA score. The mean risk of developing major postoperative complications was 7% in patients with score 0 to 3, 13% in patients with score 4 to 7, 23% in patients with score 8 to 11, and 36% in patients with score 12 to 15. In the validation population, the predicted risk of major complications was 15.2% versus a 16.9% observed risk (C-statistic index = 0.743).
This new score may accurately predict a patient's postoperative outcome. Early identification of high-risk patients could help the surgeon to adopt intraoperative and postoperative strategies tailored on individual basis.
Recently, the term mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) has been proposed as an umbrella definition covering different possible combinations of mixed neuroendocrine-exocrine ...neoplasms. Among these, the adenoma plus neuroendocrine tumor (NET) combination is among the rarest and not formally recognized by the 2019 WHO Classification. In this setting, the debate between either collision tumors or true mixed neoplasms is still unsolved. In this report, a pancreatic intraductal papillary mucinous neoplasm (IPMN) plus a NET is described, and the molecular investigations showed the presence in both populations of the same KRAS, GNAS, and CDKN2A mutations and the amplification of the CCND1 gene. These data prove clonality and support a common origin of both components, therefore confirming the true mixed nature. For this reason, mixed neuroendocrine-exocrine neoplasms, in which the exocrine component is represented by a glandular precursor lesion (adenoma/IPMN) only, should be included into the MiNEN family.
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