[Ethical, legal and social implications in the use of artificial intelligence-based technologies in surgery : Principles, implementation and importance for the user].

Ethical, legal and social aspects are gaining increasingly more attention in the development and during the initial clinical application of medical devices. The introduction of elements of artificial intelligence (AI) and systems which are using AI makes this already complex topic even more challenging. The introduction of so-called dynamic AI or dynamic machine learning (ML) algorithms in this respect represents a turning point.

Germination of Acacia harpophylla (Brigalow) seeds in relation to soil water potential: implications for rehabilitation of a threatened ecosystem.

Initial soil water conditions play a critical role when seeding is the primary approach to revegetate post-mining areas. In some semi-arid climates, such as the Brigalow Belt Bioregion in eastern Australia, extensive areas are affected by open-cut mining. Together with erratic rainfall patterns and clayey soils, the Brigalow Belt denotes a unique biome which is representative of other water-limited ecosystems worldwide.

Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

Purpose: Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations.

Patients And Methods: Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors.

A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry.

Mismatch repair (MMR) gene sequence variants of uncertain clinical significance are often identified in suspected Lynch syndrome families, and this constitutes a challenge for both researchers and clinicians. Multifactorial likelihood model approaches provide a quantitative measure of MMR variant pathogenicity, but first require input of likelihood ratios (LRs) for different MMR variation-associated characteristics from appropriate, well-characterized reference datasets. Microsatellite instability (MSI) and somatic BRAF tumor data for unselected colorectal cancer probands of known pathogenic variant status were used to derive LRs for tumor characteristics using the Colon Cancer Family Registry (CFR) resource.

Immunohistochemical testing of conventional adenomas for loss of expression of mismatch repair proteins in Lynch syndrome mutation carriers: a case series from the Australasian site of the colon cancer family registry.

Debate continues as to the usefulness of assessing adenomas for loss of mismatch repair protein expression to identify individuals with suspected Lynch syndrome. We tested 109 polyps from 69 proven mutation carriers (35 females and 34 males) belonging to 49 Lynch syndrome families. All polyps were tested by immunohistochemistry for four mismatch repair proteins MLH1, MSH2, MSH6 and PMS2.

Integration of a 3D ultrasound probe into neuronavigation.

Background: Intraoperative ultrasound (iUS) allows the generation of real-time data sets during surgical interventions. The recent innovation of 3D ultrasound probes permits the acquisition of 3D data sets without the need to reconstruct the volume by 2D slices. This article describes the integration of a tracked 3D ultrasound probe into a neuronavigation.

Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry.

Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families.

Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing.

Risks of Lynch syndrome cancers for MSH6 mutation carriers.

Background: Germline mutations in MSH6 account for 10%-20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain.

Methods: We identified 113 families of MSH6 mutation carriers from five countries that we ascertained through family cancer clinics and population-based cancer registries.

Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics.

Reliable methods for predicting functional consequences of variants in disease genes would be beneficial in the clinical setting. This study was undertaken to predict, and confirm in vitro, splicing aberrations associated with mismatch repair (MMR) variants identified in familial colon cancer patients. Six programs were used to predict the effect of 13 MLH1 and 6 MSH2 gene variants on pre-mRNA splicing.

Analysis of families with Lynch syndrome complicated by advanced serrated neoplasia: the importance of pathology review and pedigree analysis.

The identification of Lynch syndrome has been greatly assisted by the advent of tumour immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and by the recognition of the role of acquired somatic BRAF mutation in sporadic MMR-deficient colorectal cancer (CRC). However, somatic BRAF mutation may also be present in the tumours in families with a predisposition to develop serrated polyps in the colorectum. In a subgroup of affected members in these families, CRCs emerge which demonstrate clear evidence of MMR deficiency with absent MLH1 staining and high-level microsatellite instability (MSI).

Molecular, pathologic, and clinical features of early-onset endometrial cancer: identifying presumptive Lynch syndrome patients.

Purpose: A woman with early-onset endometrial cancer (EC) may represent the "sentinel" cancer event in a Lynch syndrome kindred. The aim of this study was to determine the incidence of Lynch syndrome in a series of young-onset EC, and to identify molecular, clinical, and pathologic features that may alert clinicians to the presence of this disorder.

Experimental Design: Patients with EC, ages < or =50 years, were identified from the Queensland Centre for Gynaecological Cancer.

Evidence for BRAF mutation and variable levels of microsatellite instability in a syndrome of familial colorectal cancer.

Background And Aims: Recently, an alternative pathway of tumorigenesis has been identified in the colorectum associated with serrated precursor lesions, variable levels of microsatellite instability (MSI-V), and driven in part by activating mutations in the BRAF proto-oncogene (V599E). Somatic BRAF mutations in hereditary nonpolyposis colon cancer (HNPCC) are rarely observed. Here, we discuss their role in the development of other familial colorectal cancers (CRC).

Role of inherited defects of MYH in the development of sporadic colorectal cancer.

Biallelic germ-line variants of the 8-hydroxyguanine repair gene MYH have been associated with multiple colorectal adenomas that display somatic G:C-->T:A transversions in APC. However, the effect of single germ-line variants has not been widely studied. To examine the relationship between monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC), 92 cases of sporadic CRC, 19 cases of familial CRC not meeting the Bethesda guidelines, 17 cases with multiple adenomas, and 53 normal blood donors were screened for 8 potentially pathogenic germ-line MYH variants.

Iterative neuronavigation using 3D ultrasound. A feasibility study.

Intra-operative ultrasound (iUS) can generate 2D images in real-time as well as near real-time 3D datasets of the current situation during an intervention. Tracked ultrasound can locate the images in 3D space and relate them to patient, devices, andpre-operative planning data. Therefore, tracked US is an efficient means for controlling the validity of pre-operative planning, recognition of changes (brain shift) during the intervention, replanning of the operational path due to situational changes (iterative navigation), and finally, controlling the results (residual tumor).