Morphology Matters: A Critical Reappraisal of the Clinical Relevance of Morphologic Criteria From the 2019 WHO Classification in a Large Colorectal Cancer Cohort Comprising 1004 Cases.

The 2019 World Health Organization (WHO) classification of colorectal carcinoma (CRC) profoundly reclassified CRC subtypes and introduces tumor budding as a second major grading criterion, while condensing conventional grade into a 2-tiered system. So far it remains largely unexplored how these parameters interact with each other and whether they truly have an independent impact on patient prognosis. We reclassified a large single-center cohort of 1004 CRCs spanning 2 decades for adjusted WHO grade (low vs. high), tumor budding (Bd1/Bd2/Bd3), and CRC subtype (adenocarcinoma not otherwise specified, micropapillary, mucinous, serrated, medullary, adenoma-like, signet-ring cell, mixed adenoneuroendocrine carcinoma/neuroendocrine carcinoma, undifferentiated) according to the criteria of the 2019 WHO classification. We investigated the interaction of these parameters, their connection to stage/microsatellite status, and their significance for patient survival in the different subgroups. Specific subtypes other than adenocarcinoma not otherwise specified represented one third of all CRCs and were unevenly distributed throughout stage and microsatellite subgroups. Subtypes, WHO grade and tumor budding profoundly impacted all survival parameters (P<0.001 for all analyses), with CRC subtypes and tumor budding-but not WHO grade-being stage-independent prognosticators for all survival comparisons. WHO grade had very limited prognostic value in CRC subtypes, while tumor budding retained its strong prognostic impact in most scenarios. Accurate delineation of CRC subtypes introduced in the 2019 WHO classification provides strong stage-independent prognostic information, arguing that they should be considered in pathology reports and in clinical trials. Of the morphology-based grading schemes included in the 2019 WHO, tumor budding outperforms WHO grade.

On the Feasibility of Fan-Out Wafer-Level Packaging of Capacitive Micromachined Ultrasound Transducers (CMUT) by Using Inkjet-Printed Redistribution Layers.

Fan-out wafer-level packaging (FOWLP) is an interesting platform for Microelectromechanical systems (MEMS) sensor packaging. Employing FOWLP for MEMS sensor packaging has some unique challenges, while some originate merely from the fabrication of redistribution layers (RDL). For instance, it is crucial to protect the delicate structures and fragile membranes during RDL formation. Thus, additive manufacturing (AM) for RDL formation seems to be an auspicious approach, as those challenges are conquered by principle. In this study, by exploiting the benefits of AM, RDLs for fan-out packaging of capacitive micromachined ultrasound transducers (CMUT) were realized via drop-on-demand inkjet printing technology. The long-term reliability of the printed tracks was assessed via temperature cycling tests. The effects of multilayering and implementation of an insulating ramp on the reliability of the conductive tracks were identified. Packaging-induced stresses on CMUT dies were further investigated via laser-Doppler velocimetry (LDV) measurements and the corresponding resonance frequency shift. Conclusively, the bottlenecks of the inkjet-printed RDLs for FOWLP were discussed in detail.

Genetic Biopsy for Prediction of Surveillance Intervals after Endoscopic Resection of Colonic Polyps: Results of the GENESIS Study.

BACKGROUND AND OBJECTIVE: Current surveillance strategies for colorectal cancer following polypectomy are determined by endoscopic and histopathological factors. Such a distinction has been challenged. The present study was designed to identify molecular parameters in colonic polyps potentially defining new sub-groups at risk. METHODS: One hundred patients were enrolled in this multicentre study. Polyps biopsies underwent formalin-free processing (PAXgene, PreAnalytiX) and targeted next generation sequencing (38 genes (QIAGEN), NextSeq 500 platform (Illumina)). Genetic and histopathological analyses were done blinded to other data. RESULTS: In 100 patients, 224 polyps were removed. Significant associations of genetic alterations with endoscopic or histological polyp characteristics were observed for BRAF, KRAS, TCF7L2, FBXW7 and CTNNB1 mutations. Multivariate analysis revealed that polyps ≥ 10 mm have a significant higher relative risk for harbouring oncogene mutations (relative risk 3.467 (1.742-6.933)). Adenomas and right-sided polyps are independent risk factors for CTNNB1 mutations (relative risk 18.559 (2.371-145.245) and 12.987 (1.637-100.00)). CONCLUSIONS: Assessment of the mutational landscape of polyps can be integrated in the workflow of current colonoscopy practice. There are distinct genetic patterns related to polyp size and location. These results suffice to optimise individual risk calculation and may help to better define surveillance intervals.