Influence of perioperative step volume on complication rate and length of hospital stay after colorectal cancer surgery (IPOS trial): study protocol for a randomised controlled single-centre trial at a German university hospital

Background Perioperative mobilisation and physical activity are critical components of postoperative rehabilitation. Physical inactivity is a significant risk factor for complications and prolonged hospitalisation. However, specific recommendations for preoperative and postoperative physical activity levels are currently lacking. Evidence suggests that daily step count before and after surgery may impact the length of hospital stay and complication rate. The goal of this study is to determine the effectiveness of perioperative step volume recommendations, measured by pedometers, in reducing the length of hospital stay and complication rate for patients undergoing colorectal cancer surgery. Methods This study is a single-centre randomised controlled trial with two arms, allocated at a 1:1 ratio. The trial includes individuals undergoing colorectal surgery for either suspected or confirmed colorectal malignancy. A total of 222 patients will be randomly assigned to either an intervention or a control group. Step counts will be measured using a pedometer. Patients assigned to the intervention group will be given a predetermined preoperative and postoperative step count goal. The analysis will be conducted on preoperative and postoperative physical activity, quality of life, health, duration of hospitalisation, complication rate and bowel function, among other factors. Ethics and dissemination The trial was approved by the ethics committee of the Ludwig-Maximilians-University of Munich, Germany (reference number: 22-0758, protocol version 2022.02). Results will be published in peer-reviewed journals and shared at academic conferences. After the publication of the results, a fully anonymised data set and the statistical code can be made available on justified scientific request and after ethical approval has been granted. Trial registration number DRKS00030017

Single Chromosome Aneuploidy Induces Genome-Wide Perturbation of Nuclear Organization and Gene Expression

Chromosomal aneuploidy is a defining feature of carcinomas and results in tumor-entity specific genomic imbalances. For instance, most sporadic colorectal carcinomas carry extra copies of chromosome 7, an aneuploidy that emerges already in premalignant adenomas, and is maintained throughout tumor progression and in derived cell lines. A comprehensive understanding on how chromosomal aneuploidy affects nuclear organization and gene expression, i.e., the nucleome, remains elusive. We now analyzed a cell line established from healthy colon mucosa with a normal karyotype (46,XY) and its isogenic derived cell line that acquired an extra copy of chromosome 7 as its sole anomaly (47,XY,+7). We studied structure/function relationships consequent to aneuploidization using genome-wide chromosome conformation capture (Hi-C), RNA sequencing and protein profiling. The gain of chromosome 7 resulted in an increase of transcript levels of resident genes as well as genome-wide gene and protein expression changes. The Hi-C analysis showed that the extra copy of chromosome 7 is reflected in more interchromosomal contacts between the triploid chromosomes. Chromatin organization changes are observed genome-wide, as determined by changes in A/B compartmentalization and topologically associating domain (TAD) boundaries. Most notably, chromosome 4 shows a profound loss of chromatin organization, and chromosome 14 contains a large A/B compartment switch region, concurrent with resident gene expression changes. No changes to the nuclear position of the additional chromosome 7 territory were observed when measuring distances of chromosome painting probes by interphase FISH. Genome and protein data showed enrichment in signaling pathways crucial for malignant transformation, such as the HGF/MET-axis. We conclude that a specific chromosomal aneuploidy has profound impact on nuclear structure and function, both locally and genome-wide. Our study provides a benchmark for the analysis of cancer nucleomes with complex karyotypes