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The majority of patients treated in our centre were women, middle-aged patients booked for elective laparoscopic cholecystectomy. Although only 6.7% cases were suspicious for CBD stones pre-operatively, a total of 17% of patients with routine IOC suggested CBD stones. IOC was found to be safe, taking only an additional 28 min of total theatre time. Routine rather than selective use of IOC could be considered to improve patient safety and long-term results.

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The Plant Homeodomain 6 gene (PHF6) encodes a nucleolar and chromatin-associated leukemia tumor suppressor with proposed roles in transcription regulation. However, specific molecular mechanisms controlled by PHF6 remain rudimentarily understood. Here we show that PHF6 engages multiple nucleosome remodeling protein complexes including NuRD, SWI/SNF and ISWI factors, the replication machinery and DNA repair proteins. Moreover, following DNA damage, PHF6 localizes to sites of DNA injury and its loss impairs the resolution of DNA breaks with consequent accumulation of single- and double-stranded DNA lesions. Native chromatin immunoprecipitation sequencing analyses reveal that PHF6 specifically associates with difficult to replicate heterochromatin at satellite DNA regions enriched in Histone H3 lysine 9 trimethyl marks (H3K9me3) and single molecule locus-specific analyses identify PHF6 as an important regulator of genomic stability at fragile sites. These results extend our understanding of the molecular mechanisms controlling HSC homeostasis and leukemia transformation by placing PHF6 at the crossroads of chromatin remodeling, replicative fork dynamics and DNA repair.

Background Laparoscopic colorectal cancer surgery has been shown to produce comparable oncological long‐term results as well as improved short‐term outcomes compared to open surgery in multicentre trials. Limited information is available whether these results are reproduced in non‐metropolitan surgery. Methods Audit of prospectively collected follow‐up data in a rural surgical centre in South Australia. Short‐ and long‐term results of colorectal cancer patients undergoing elective laparoscopic surgery for cure. Outcomes are compared with results of open surgery. Results Survival and clinical data of 120 patients after laparoscopic resection were analysed and then benchmarked against results of 157 open resections. Conversion rate was 10.8% (N = 13). Mean patient age was 69.9 years. Mean number of lymph nodes analysed was 15.5. Mean follow‐up is 53.0 months. Thirty‐day mortality was 0.36% (n = 1) and 90‐day mortality was 0.72% (n = 2). No differences in complications rates, long term survival or procedures performed were observed. This is a single centre audit of clinical and oncological outcomes and a number of exclusion criteria were applied. Patient gender, cancer stages as well as number of patients undergoing neoadjuvant radio‐chemotherapy differ significantly between the study and the benchmarking group. Patients were not randomized and the benchmarking group is in part a historical control. Conclusions This audit of clinical outcomes and survival after laparoscopic CRC resection for cure indicates that minimal invasive surgery may be suitable for adequately staffed and equipped rural centres.

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Eukaryotes undergo transcription and splicing simultaneously, allowing for coordination and regulation of these two processes. Currently, there are a few known connections between chromatin modification, which regulates transcription, and splicing found in yeast and metazoa1,2, yet there is still much to study. The NuA4 histone acetyltransferase works with Swr1 chromatin remodeling enzyme to promote transcription3–5. First, NuA4 acetylates histone H4, which is required for the recruitment of Swr1. Next, Swr1 inserts the histone variant H2A.Z, which is subsequently acetylated by NuA4. Interestingly, in Saccharomyces cerevisiae, both NuA4 and Swr1 play a key role in the transcription of the ribosomal protein genes7, which make up a large fraction of the intron containing genes. Thus, NuA4, Swr1, and H2A.Z are excellent candidates for coordinating transcription and splicing. A role for H2A.Z in splicing was recently identified6. Interestingly, data from our lab suggest that NuA4 may have functions in RNA splicing that are independent of H2A.Z deposition. Using directed genetic screens we identified positive (suppressive) interactions between splicing factor gene mutations and mutations that catalytically inactivate NuA4. Additionally, using MPE‐seq8 and RT‐qPCR we found that mutations that block the catalytic activity of NuA4 alter the splicing of a subset of RNAs. Our data suggest that NuA4 plays a role in regulating RNA splicing and we are currently performing chromatin immunoprecipitation experiments to determine whether ESA1 catalytic activity impacts the association of splicing proteins with nascent RNAs during transcription. Together, our data support a model in which NuA4 interacts with the splicing machinery to coordinate transcription and splicing.Support or Funding InformationResearch Corporation for the Advancement of Science (Cottrell College Science award no. 20186) National Institutes of Health (R15GM122026).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.