Complex Patterns of Genomic Heterogeneity Identified in 42 Tumor Samples and ctDNA of a Pulmonary Atypical Carcinoid Patient.

Tumor evolution underlies many challenges facing precision oncology, and improving our understanding has the potential to improve clinical care. This study represents a rare opportunity to study tumor heterogeneity and evolution in a patient with an understudied cancer type. A patient with pulmonary atypical carcinoid, a neuroendocrine tumor, metastatic to 90 sites, requested and consented to donate tissues for research. 42 tumor samples collected at rapid autopsy from 14 anatomically distinct sites were analyzed through DNA whole-exome sequencing and RNA sequencing, and five analyzed through linked-read sequencing. Targeted DNA sequencing was completed on two clinical tissue biopsies and one blood plasma sample. Chromosomal alterations and gene variants accumulated over time, and specific chromosomal alterations preceded the single predicted gene driver variant (ARID1A). At the time of autopsy, all sites shared the gain of one copy of Chr 5, loss of one copy of Chr 6 and 21, chromothripsis of one copy of Chr 11, and 39 small variants. Two tumor clones (carrying additional variants) were detected at metastatic sites, and occasionally in different regions of the same organ (e.g., within the pancreas). Circulating tumor DNA (ctDNA) sequencing detected shared tumor variants in the blood plasma and captured marked genomic heterogeneity, including all metastatic clones but few private tumor variants. This study describes genomic tumor evolution and dissemination of a pulmonary atypical carcinoid donated by a single generous patient. It highlights the critical role of chromosomal alterations in tumor initiation and explores the potential of ctDNA analysis to represent genomically heterogeneous disease. Significance: DNA sequencing data from tumor samples and blood plasma from a single patient highlighted the critical early role of chromosomal alterations in atypical carcinoid tumor development. Common tumor variants were readily detected in the blood plasma, unlike emerging tumor variants, which has implications for using ctDNA to capture cancer evolution.

Computed tomography colonography: Retrospective comparison of laxative plus barium tagging versus iodinated contrast only for bowel preparation and faecal tagging.

INTRODUCTION: There is no consensus as to the most optimal bowel preparation regime for Computed Tomographic Colonography (CTC). Concerns regarding laxative bowel preparation (LBP) include tolerability, adverse effects and complexity of regimen. Two hospitals in Auckland changed CTC bowel preparation from standard LBP to Gastrografin (GG) in 2015. The aim of this study is to retrospectively assess objective and subjective quality measures of these different bowel preparations. METHODS: Two study groups were selected retrospectively from patients who underwent CTC at two hospitals in September-October 2013 (LBP) and September- October 2015 (GG). Each study group comprised 60 patients (30 consecutive patients from each hospital). Patients were randomized and anonymized to reduce bias in analysis. Study patients were assessed independently by three experienced Radiologists using a simple grading system derived from the literature. RESULTS: There was significantly less faecal residue (P = 0.006) and better faecal tagging (P = 0.001) in the right colon in the GG group. There was significantly higher fluid residue in the GG group than the LBP group (P = 0.0001), particularly in the right colon, with better fluid tagging in the GG group(P ≤ 0.0001). Higher Hounsfield Units of residual fluid were observed in the GG group (P ≤ 0.0001). There was no statistically significant difference in the subjective quality scores (P = 0.219), between the two preparations. CONCLUSIONS: This study has demonstrated better faecal cleansing and faecal tagging in the GG group. Higher fluid residue in the GG group was offset by better fluid tagging.