Explore the vast range of titles available.

Summarises the ethical, logistical and social process undertaken to accept a patient's donation of tumour tissues post-mortem, and highlights the scientific and educational value of such a gift. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report the analysis of gene mutation, copy number, and RNA expression of 57 sporadic well-differentiated pNETs. pNET genomes are dominated by aneuploidy, leading to concordant changes in RNA expression at the level of whole chromosomes and chromosome segments. We observed two distinct patterns of somatic pNET aneuploidy that are associated with tumor pathology and patient prognosis. Approximately 26% of the patients in this series had pNETs with genomes characterized by recurrent loss of heterozygosity (LoH) of 10 specific chromosomes, accompanied by bi-allelic MEN1 inactivation and generally poor clinical outcome. Another ~40% of patients had pNETs that lacked this recurrent LoH pattern but had chromosome 11 LoH, bi-allelic MEN1 inactivation, and universally good clinical outcome. The somatic aneuploidy allowed pathogenic germline variants (e.g., ATM) to be expressed unopposed, with RNA expression patterns showing inactivation of downstream tumor suppressor pathways. No prognostic associations were found with tumor morphology, single gene mutation, or expression of RNAs reflecting the activity of immune, differentiation, proliferative or tumor suppressor pathways. In pNETs, single gene mutations appear to be less important than aneuploidy, with MEN1 the only statistically significant recurrently mutated driver gene. In addition, only one pNET in the series had clearly actionable single nucleotide variants (SNVs) (in PTEN and FLCN) confirmed by corroborating RNA expression changes. The two clinically relevant patterns of LoH described here define a novel oncogenic mechanism and a plausible route to genomic precision oncology for this tumor type.

Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Analysis of gene mutation, copy number and RNA expression of 57 sporadic pNETs showed that pNET genomes are dominated by aneuploidy. Remarkably, ~25% of pNETs had genomes characterized by recurrent loss of heterozygosity (LoH) of the same 10 chromosomes, accompanied by bi-allelic MEN1 inactivation, and these cases had generally poor clinical outcome. Another ~25% of all pNETs had chromosome 11 LoH and bi-allelic MEN1 inactivation, lacking the recurrent LoH pattern these had universally good clinical outcome. Some level of aneuploidy was common, and overall ~80% of pNETs had LoH of 1 chromosome. This aneuploidy led to changes in RNA expression at the level of whole chromosomes and allowed pathogenic germline variants (e.g. ATM) to be expressed unopposed, inactivating downstream tumor suppressor pathways. Some pNETs appear to utilise VHL gene methylation or mutation to activate pseudo-hypoxia. Contrary to expectation neither tumor morphology within well-differentiated pNETs nor single gene mutation had significant associations with clinical outcome, nor did expression of RNAs reflecting the activity of immune, differentiation, proliferative or tumor suppressor pathways. MEN1 was the only statistically significant recurrently mutated driver gene in pNETs. Only one pNET had clearly oncogenic and actionable SNVs (in PTEN and FLCN) confirmed by corroborating RNA expression changes. The two distinct patterns of aneuploidy described here, associated with markedly poor and good clinical outcome respectively, define a novel oncogenic mechanism and the first route to genomic precision oncology for this tumor type.

BackgroundDocumentation of pregnancy status (PS) is an integral component of the assessment of women of reproductive age when admitted to hospital. Our aim was to determine how accurately PS was documented in a multicentre audit of female admissions to general surgery.MethodsA prospective multicentre audit of elective and emergency admissions was performed in 18 Scottish centres between 08:00 on 11 May 2015 and 07:59 on 25 May 2015. The lower age limit was the minimum age for admission to the adult surgical ward and the upper age limit was 55 years.ResultsThere were 2743 admissions, with 612 (22.3%) women of reproductive age. After 82 exclusions, the final total was 530: 169 (31.9%) elective and 361 (68.1%) emergency. Documentation of PS was achieved in 274 (51.7%) cases: 52 (30.8%) elective and 222 (61.5%) emergency. In 318 (88.1%) of the emergency admissions, the patient had abdominal pain. Of these, 211 (65.1%) had a documented PS. The possibility of pregnancy was established in 237 (44.7%) cases.DiscussionEstablishing the possibility of pregnancy before surgery is poor, particularly in the elective setting. Objective documentation of PS in the emergency setting in those with abdominal pain is also poor. Our study highlights an important safety issue in the management of female patients. We advocate electronic storage of pregnancy test results and new guidelines to cover both elective and emergency surgery. PS should form part of the pre-theatre safety brief and checklist.