| Background: CRC is a common malignant tumor with high morbidity and mortality.Due to the atypical early symptoms,most are in the middle and late stage when they are discovered.Obstruction is a common complication of advanced CRC.Such colorectal cancer patients with intestinal obstruction(CRCIO)are often complicated with severe malnutrition,metabolic disorders,and acid-base imbalances.The treatment should first relieve the obstruction.The traditional methods include surgery and stent placement.Surgery is risky and often requires a fistula,which seriously affects the patient’s quality of life.Simple stent placement faces a high rate of re-obstruction.Therefore,there is an urgent need for more effective treatment modalities to improve efficacy.Objective: This study is to evaluate the clinical efficacy and safety of metal stent combined with PDT in CRCIO and to analyze the related factors that affect the efficacy of PDT and patient survival.To investigate the effect of PDT on intestinal flora and gene expression in CRC.Methods:(1)The clinical data of 50 patients with stage Ⅲ-Ⅳ CRCIO treated in the Cancer Center of Lanzhou University Second Hospital from November 2019 to November 2022 were retrospectively analyzed.The included patients were divided into two groups according to whether PDT was combined,metal stent group(Stent)and PDT combined metal stent group(PDT+Stent).The curative effect and survival were compared between the groups,and the relevant factors that affected the curative effect of PDT and the survival of patients were analyzed.(2)Collect fresh stool samples from patients before and after PDT,and use 16 S r RNA high-throughput sequencing to detect the changes in intestinal flora before and after PDT.(3)The gene expression changes in CRC patients’ tumour tissues before PDT and 48 hours after PDT were evaluated by transcriptome sequencing.Results:(1)16 patients were included in the Stent group,and 34 patients were included in the PDT+Stent group.There were no significant differences in the essential clinicopathological characteristics between the two groups,including age,sex,tumor location,clinical stage,degree of tumor differentiation,BMI,and KPS score,whether combined with systemic anticancer drug therapy.Regarding short-term curative effects,all 50 patients in the two groups underwent intestinal stent placement and/or PDT,and all 50 patients achieved technical success.12(75.0%)in the Stent group achieved clinical success,and 30(88.2%)patients in the PDT+Stent group achieved clinical success.The difference was not statistically significant(P=0.249).There were no significant differences in the stent patency rate(2 months after placement),objective response rate,tumor markers,hemoglobin,albumin,BMI,etc.,between the two groups(P>0.05).The disease control rate(64.7% vs 31.3%,P=0.027)and KPS score increase(15 vs 10,P=0.001)of the PDT+Stent group were higher than the Stent group.KPS score and degree of tumor necrosis after PDT were two indicators affecting the shortterm curative effect of patients in the PDT+Stent group,and patients with KPS≥80points(P<0.05)and moderate to severe necrosis after PDT(P<0.05)had a better curative effect.Regarding long-term efficacy,the stent patency rate(6 months after placement)of the PDT+Stent group was higher than that of the Stent group(81.3% vs50.0%,P<0.05),and there was no significant difference in the clinical success rate.The median survival time of 50 patients was 16(95%CI [12-19])months.The median survival time of the PDT+Stent group and Stent group were 18(95%CI [14-24])months and 12(95%CI [9-19])months,respectively(HR=0.49,95%CI [0.25-0.98],P=0.045),the overall survival of the PDT+Stent group was significantly better than that of the Stent group.Univariate analysis showed that the degree of tumor necrosis after PDT,KPS score,and whether combined with drug therapy were related to the overall survival of patients.Patients with moderate to severe necrosis after PDT(P=0.043),KPS≥80points(P=0.029)and combined drug therapy(P=0.025)patients had longer overall survival.Further analysis by multivariate COX showed that whether combined with drug therapy and the clinical stage of patients were independent risk factors affecting the overall survival of CRCIO in the PDT+ST group.In terms of safety,the adverse events and incidence rates were abdominal pain(36.0%),leukocytosis(20.6%),fever(11.8%),nausea and vomiting(6.0%),bleeding(6.0%),skin phototoxicity(2.9%),Stent displacement(2.0%),no serious adverse events occurred.(2)Alpha diversity analysis showed no significant difference in the richness and diversity of intestinal microbial communities before and after PDT(P>0.05).In terms of species composition,the OTU analysis showed 399 OTU(species)in the samples before PDT,483 OTU after PDT,and 267 OTUs in common,indicating that the species composition of the two samples before and after PDT changed.Overall,the top three dominant genera were: Bacteroides,Escherichia,and Lactobacillus.After further comparing the differences in species abundance between the two groups before and after PDT,it was found that in the sample microbial community after PDT,the relative abundance of bifidobacterium,mycobacterium,christensen,eubacterium,and ruminococcus increased significantly(P<0.05).(3)PDT caused changes in gene expression,and a total of 2874 differential genes were screened out,of which 1889 were up-regulated,and 985 were down-regulated.GO enrichment analysis showed that differentially expressed genes involved multiple biological processes,such as cell transformation,biological regulation,and metabolic processes.KEGG enrichment analysis showed that differential genes were significantly enriched in the IL-17 signaling pathway,complement system,MAPK signaling pathway,and TNF signaling pathway,which may affect the immune process and the occurrence and development of CRC.Conclusions:(1)In patients with CRCIO,metal stent combined with PDT is superior to metal stent therapy and has better clinical efficacy and safety.(2)Based on PDT combined with metal stents,further combined with systemic anticancer drug therapy can benefit patients’ survival.(3)PDT caused changes in the species composition of intestinal flora,and PDT may improve the efficacy of immunotherapy by increasing the abundance of intestinal bifidobacteria.The abundance of various intestinal probiotic species increased after PDT,which may improve the microenvironment of intestinal flora.(4)PDT can significantly affect the expression of CRC transcriptome,which provides a new idea for the in-depth study of the mechanism of PDT in CRC treatment and the optimization of treatment options. |
