Merits and Faults of Transanal Ileus Tube for Obstructing Colorectal Cancer

BackgroundWe report eight cases of obstructing colorectal cancer successfully managed by pre-operative lavage using transanal ileus tube.MethodsDecompression tube was transanally inserted into the colon proximal to the tumour under the guidance of the guide wire. Intestinal lavage with 1,500-2,000 mL of warm water was done every day until surgery.ResultsThere were six men and two women; the mean age was 67 years (range, 50-82 years). Three cancers were in the sigmoid colon and five were in the rectum. Seven patients were treated with a one-stage operation with adequate lymph node dissection. In one patient, only sigmoidostomy was carried out for unresectable huge tumour. In all cases, no dilatation was observed at the proximal colon and no anastomotic failure developed. Four patients suffered from fever of unknown cause after the insertion of the tube. In one patient, the resected specimen showed ulcer by tube compression. In the other patient, the tube penetrated the intestinal wall, which was covered by mesentery.ConclusionThe transanal ileus tube is effective for the treatment of obstructing colorectal cancer. However, close observation is necessary because of possible perforation

The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis

Abstract The ubiquitin‒proteasome system (UPS) and autophagy are the two primary cellular pathways of misfolded or damaged protein degradation that maintain cellular proteostasis. When the proteasome is dysfunctional, cells compensate for impaired protein clearance by activating aggrephagy, a type of selective autophagy, to eliminate ubiquitinated protein aggregates; however, the molecular mechanisms by which impaired proteasome function activates aggrephagy remain poorly understood. Here, we demonstrate that activation of aggrephagy is transcriptionally induced by the transcription factor NRF1 (NFE2L1) in response to proteasome dysfunction. Although NRF1 has been previously shown to induce the expression of proteasome genes after proteasome inhibition (i.e., the proteasome bounce-back response), our genome-wide transcriptome analyses identified autophagy-related p62/SQSTM1 and GABARAPL1 as genes directly targeted by NRF1. Intriguingly, NRF1 was also found to be indispensable for the formation of p62-positive puncta and their colocalization with ULK1 and TBK1, which play roles in p62 activation via phosphorylation. Consistently, NRF1 knockdown substantially reduced the phosphorylation rate of Ser403 in p62. Finally, NRF1 selectively upregulated the expression of GABARAPL1, an ATG8 family gene, to induce the clearance of ubiquitinated proteins. Our findings highlight the discovery of an activation mechanism underlying NRF1-mediated aggrephagy through gene regulation when proteasome activity is impaired