Stent placement in Obstructive Colorectal Cancer Changing Blood and Tissue Biomarkers
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasms
PROVIDER: 2509139 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Colorectal cancer is the fourth most common cancer in China. Up to 30% of patients with colorectal cancer present with an emergency obstruction of the large bowel at the time of diagnosis, and 70% of all malignant obstruction occurs in the left-sided colon. Patients with obstruction are associated with worse oncologic outcomes compared with those having nonobstructive tumors. Conventionally, patients with malignant large bowel obstruction receive emergency surgery, with morbidity rates of 30%-60% and mortality rates of 7-22%, and about two-thirds of such patients end up with a permanent stoma.
Self-expanding metallic stents (SEMS) haven been used as a bridge to surgery (to relieve obstruction prior to elective surgery) in patients with potentially resectable colorectal cancer. Several clinical trials demonstrate that SEMS as a bridge to surgery may be superior to emergency surgery considering the short-term outcomes. SEMS is associated with lower morbidity and mortality rate, increased primary anastomosis rate, and decreased stoma creation rate. Although about half of patients can achieve primary anastomosis after stent placement, the primary anastomosis rate is still significantly lower compared with nonobstructing elective surgery. The interval between stent placement and surgery may be not long enough that bowel decompression is insufficient at the time of operation. Furthermore，the long-term oncologic results regarding SEMS as a bridge to surgery are still limited and contradictory. Sabbagh et al. suggest worse overall survival of patients with SEMS insertion compared with emergency surgery, the 5-year cancer-specific mortality was significantly higher in the SEMS group (48% vs 21%, respectively, P=0.02). One interpretation is that tumor cells may disseminate during the procedure of colonic stenting placement. We hypothesis that immediate chemotherapy after stenting may improve overall survival by eradicating micrometastasis. Moreover, neoadjuvant chemotherapy prolongs the interval between stent placement and surgery, and the time for bowel decompression is more sufficient, which may increase the success rate of primary anastomosis and decrease risk of stoma formation.
| 2230508 | ecrin-mdr-crc
Project description:Patients with obstruction are associated with worse oncologic outcomes compared with those having nonobstructive tumors. Conventionally, patients with malignant large bowel obstruction receive emergency surgery, with morbidity rates of 30%-60% and mortality rates of 7-22%, and about two-thirds of such patients end up with a permanent stoma. Self-expanding metallic stents (SEMS) haven been used as a bridge to surgery (to relieve obstruction prior to elective surgery) in patients with potentially resectable colorectal cancer. Several clinical trials demonstrate that SEMS as a bridge to surgery may be superior to emergency surgery considering the short-term outcomes. SEMS is associated with lower morbidity and mortality rate, increased primary anastomosis rate, and decreased stoma creation rate. Although about half of patients can achieve primary anastomosis after stent placement, the primary anastomosis rate is still significantly lower compared with nonobstructing elective surgery. The interval between stent placement and surgery may be not long enough that bowel decompression is insufficient at the time of operation. Furthermore#the long-term oncologic results regarding SEMS as a bridge to surgery are still limited and contradictory. Sabbagh et al. suggest worse overall survival of patients with SEMS insertion compared with emergency surgery, the 5-year cancer-specific mortality was significantly higher in the SEMS group (48% vs 21%, respectively, P=0.02). One interpretation is that tumor cells may disseminate during the procedure of colonic stenting placement. Immunotherapy has proven to be highly effective as first-line treatment of metastatic colorectal cancer (CRC). And immunotherapy also has emerged as a neoadjuvant approach, possibly changing treatment strategy for both primary resectable and metastatic CRC. We hypothesis that, regardless of the MSI state, immunotherapy (Camrelizumab, an anti-PD-1 antibody) combined with chemotherapy after stenting may improve overall survival by eradicating micrometastasis. Moreover, immunotherapy (Camrelizumab, an anti-PD-1 antibody) combined with neoadjuvant chemotherapy prolongs the interval between stent placement and surgery, and the time for bowel decompression is more sufficient, which may increase the success rate of primary anastomosis and decrease risk of stoma formation, and furthermore, improve OS and PFS.
| 2401796 | ecrin-mdr-crc
Project description: Not available
| S-EPMC8382984 | biostudies-literature
Project description:Epithelial-mesenchymal transition (EMT) is initiated and regulated by a transcriptional reprogramming in response to microenvironmental cues. How cancer cells overcome the lack of such cues during the metastatic journey remains unclear. Here we report a novel positive-feedback loop of EMT that maintains the mesenchymal traits of cancer cells during metastasis. Using subgenome-wide screening, we identified KLHL23 as a tumor invasion suppressor, which binds to actin and suppresses actin-filament formation. Silencing or ectopic expression of KLHL23 induces EMT or MET (mesenchymal-epithelial transition), respectively, through its action on actin dynamics. Increased actin-dynamics by silencing KLHL23 or treatment with F-actin disruptors or inducers enhances the EMT transcriptional reprogramming via the induction of ROS, HIF-1a, HIF-2a and NOTCH signalling pathways in cancer cells under stress or ongoing EMT. Downregulation of KLHL23 is found in human liver and pancreatic cancers and associated with tumor metastasis and poor prognosis.
2016-11-01 | GSE74996 | GEO
Project description:INTRODUCTION: There are several alternatives for one-stage emergency treatment of obstructive left-sided colonic cancer (OLCC): subtotal colectomy, intraoperative colon lavage (IOCL) with primary anastomosis, and the placement of a stent as a temporary measure prior to scheduled surgery. At present, it is not clear whether emergency perioperative lavage or the placement of a stent is the better technique. The hypothesis is that IOCL and primary anastomosis is equal safe or even safer than placement of a stent as a temporary measure prior to scheduled surgery, less length of stay and less cost.
OBJECTIVE: To establish which of these two techniques is more efficient in OLCC from the point of view of morbimortality, economic cost, and long-term survival.
MATERIAL AND METHODS:
Prospective, controlled, randomized study of patients diagnosed with OLCC. Patients were divided into two groups: group 1: stent and deferred surgery; group 2: emergency IOCL. A simple randomization system was used. The estimated sample size required per group was 21 patients. Demographic variables, risk prediction models, postoperative morbimortality, staging, complications due to the placement of stent, surgical time, clinical follow-up, health costs and follow-up of survival were recorded.
| 2094686 | ecrin-mdr-crc
Project description:Epithelial to Mesenchymal Transition (EMT) has been associated with cancer cell heterogeneity, plasticity and metastasis. It has been the subject of several modeling effort. This logical model of the EMT cellular network aims to assess microenvironmental signals controlling cancer-associated phenotypes amid the EMT continuum. Its outcomes relate to the qualitative degrees of cell adhesions by adherent junctions and focal adhesions, two features affected during EMT. Model attractors recover epithelial, mesenchymal and hybrid phenotypes, and simulations show that hybrid phenotypes may arise through independent molecular paths, involving stringent extrinsic signals.
Of particular interest, model predictions and their experimental validations indicated that: 1) ECM stiffening is a prerequisite for cells overactivating FAK-SRC to upregulate SNAIL1 and acquire a mesenchymal phenotype, and 2) FAK-SRC inhibition of cell-cell contacts through the Receptor Protein Tyrosine Phosphates kappa leads to the acquisition of a full mesenchymal rather than a hybrid phenotype.
2020-06-30 | MODEL2004040001 | BioModels
Project description: Not available
| S-EPMC8274650 | biostudies-literature
Project description:Symptoms including pain and discomfort commonly present during ureteral stenting is not well understood. We investigated global changes in ureters at the transcriptional, translational, and functional levels while stents are indwelling and following removal and recovery using a porcine model. Polaris stents (6Fr, Boston Scientific, Natick, MA) were cystoscopically inserted with placement confirmed using fluoroscopy. For proteomics samples, ureters were stented for 14 days and recovered for 7 days and each pig was stented unilaterally so that the contralateral unstented kidney and ureter served as an internal control.
2023-05-10 | PXD038161 | Pride
Project description:HIF-1a and HIF-2a are expressed at high levels in mesenchymal progenitors compared to more committed mesenchymal cells and hematopoietic cells. HIF-factors could therefore have a role in the regulation the biology of mesenchymal progenitors and their functions, like the non cell-autonomous maintenance of hematopoietic progenitors. We used microarrays to detail the global program of gene expression regulated by HIF-1a or HIF-2a in mesenchymal progenitors Mesenchymal progenitors were FACS-sorted and cultured in low oxygen concentration for few days. Once cells started to form CFU-F colonies, we transduced them with shRNAs targeting specifically HIF-1a or HIF-2a. Four days after transduction, cells were collected and RNA extracted for microarray analysis.
2014-03-25 | E-GEOD-56141 | biostudies-arrayexpress
Project description: Not available
| S-EPMC5025312 | biostudies-other