Colorectal cancer (CRC) has been a common malignant tumor in China. Through the great effort in cancer prevention and treatment, the 5-year survival rate of patients with CRC in China has been largely improved. However, insufficient early diagnosis and treatment have seriously impeded the prognosis of Chinese CRC patients. The Early Diagnosis and Treatment Group of the Chinese Medical Association, Oncology Branch organized experts in the area of CRC to write the Expert Consensus on the Early Diagnosis and Treatment of Colorectal Cancer in China and issued it publicly (2020 edition). The 2020 edition of expert consensus has been meaningful to the early diagnosis and standardized treatment of CRC. Based on the prior edition, the Early Diagnosis and Treatment Group of the Chinese Medical Association, Oncology Branch revise the consensus focused on the early screening and diagnosis protocols for colorectal cancer, endoscopic/surgical management of early colorectal tumor, as well as adjuvant treatment and remedial measures and follow-up monitoring protocols. The 2023 edition of the consensus not only synthesized the latest evidence from China and combined it with the specific national condition and clinical practice, but also referred to the international guidelines. This 2023 edition consensus, developed for clinicians working on the screening, early diagnosis and treatment for CRC, would further promote the standardization and advances in the diagnosis and treatment of CRC at the early stage in China, and improve the survival and prognosis of CRC.
To detect the integrity of cell-free DNA (cfDNA) in serum defined by the ratio of ALU247 to ALU115 content, and to investigate its clinical value and prognostic value in the first diagnosis and treatment of gastric cancer (GC) in combination with serum tumor markers.
Methods
The blood samples of 79 GC patients (GC group) admitted to the First Affiliated Hospital of Bengbu Medical College from December 2020 to June 2023 and the peripheral blood samples from 39 healthy individuals (control group) with corresponding age composition during the same period were collected, the contents of two different lengths of cfDNA (ALU115 and ALU247) were detected, and the ratio of ALU247/ALU115 were calculated to obtain the integrity of their serum cfDNA. The levels of CEA, CA19-9, CA724, CA125 and ALU247/ALU115 between the two groups were compared, the relationship between cfDNA integrity and the clinicopathological parameters of GC was observed, and the receiver operating characteristics (ROC) curve of the subjects was plotted to analyze and compare the diagnostic efficacy of CEA, CA19-9, CA724, CA125, ALU247/ALU115 and the combined test for the early stage of GC. Patients were followed up to analyze the relationship between cfDNA integrity and the prognosis.
Results
According to the maximum Jordon’s index, the area under the curve (AUC) of CEA, CA19-9, CA724, CA125, ALU247/ALU115 and combined detection as diagnostic indexes were 0.53, 0.70, 0.71, 0.61, 0.83, 0.90, when the cut-off values of the above index were selected as 4.56, 15.42, 0.32, 14.74, 0.41, 0.50 respectively. The specificity of cfDNA integrity as a tumor marker alone was higher than that of traditional tumor markers, but the sensitivity was lower than that of CA724. The sensitivity was significantly higher when cfDNA integrity was detected in combination with traditional serum tumor markers, but the specificity was slightly lower. There was no significant relationship between cfDNA integrity and survival time of GC patients (P=0.129).
Conclusion
The combination of serum cfDNA integrity and traditional serum tumor markers has certain clinical significance in the first diagnosis of GC, and liquid biopsy based on the concentration and integrity of cfDNA is expected to become a new detection method for GC.
To compare the effects of surgical and medical therapy on ineffective esophageal motility (IEM) in patients with gastroesophageal reflux diseases (GERD).
Methods
According to the inclusion and exclusion criteria, a total of 57 GERD patients with IEM met the study criteria were selected. They were 1∶2 matched by applying propensity score matching. The gastroesophageal reflux disease questionnaire (GerdQ) score, GERD-health related quality of life questionnaire (GERD-HRQL) score, esophageal dynamics before and after treatment and digestive symptoms after treatment between the two groups were compared.
Results
(1) After PSM matching, 39 patients were finally included in the study, including 13 patients undergoing laparoscopic fundoplication surgery in the operation group and 26 patients undergoing esomeprazole+mosapride regimen in the medication group. Baseline data of the two groups were balanced. (2) The GerdQ scores of patients in the operation group 1 month and 6 months after treatment were lower than those of patients in the medication group, respectively (both P<0.05). (3) The improvement in GERD-HRQL scores in the operation group at 1 month and 6 months after treatment was greater than that in the medication group (P<0.001). (4) Distal contractile integral (DCI) in the medication group was higher than the baseline value before treatment (P<0.05). Lower esophageal sphincter (LES) resting pressure, median integrated relaxation pressure 4 s (IRP4) and LES residual pressure were increased in the operation group compared to the preoperative level, with statistically differences, and the levels of which were also higher than those of the medication group during the same period (all P<0.05). (5) The incidence of dysphagia in operation group was more common than that in the medication group 1 month after treatment (P<0.001), while there was no statistical difference between the two groups in incidence of dysphagia 6 months later (P=0.593).
Conclusions
IEM exists in GERD patients with lower LES pressure and if multiple rapid swallowing tests have swallowing reserve, laparoscopic fundoplication surgery can have good short-term effect, while the long-term effect needs to be further followed up. Compared with medication treatment, laparoscopic fundoplication surgery can better improve the symptoms and quality of life of GERD patients with IEM, but it is necessary to prevent the short-term postoperative dysphagia.
To reveal the causal association between appendicectomy and colorectal anal canal malignancies, by conducting a two-sample Mendelian randomization (MR) analysis using Genome Wide Association Study (GWAS).
Methods
The single nucleotide polymorphism (SNP) data associated with appendectomy and colorectal anal malignancies were obtained from publicly published biological databases such as UK Biobank and GWAS catalog, and all aggregated data based on GWAS were analyzed. Genetic loci closely associated with appendectomy were selected as instrumental variables. MR-Egger regression method, weighting median method, inverse variance weighting method were used to make two-sample MR, and P-value was used to evaluate the causal relationship between appendectomy and the risk of colorectal and anal canal malignancy.
Results
15 SNP loci related to appendicectomy were screened, including rs106520, rs10829663, rs10849448, rs142069498, rs21525, rs2171591, rs224029, rs2326394, rs2780304, rs34236350, rs56259011, rs72827881, rs7649870, rs76896900, rs815430. Three MR analysis methods revealed that there was no causal relationship between appendicectomy and colorectal anal canal malignancies. The heterogeneity and overall pleiotropy between data were not significant (P>0.05).
Conclusion
There is no causal relationship between appendicectomy and colorectal anal canal malignancies.
To explore the value of subcutaneous drainage tube in the prevention of incisional infection after emergency laparotomy in obese patients.
Methods
140 obese patients undergoing emergency laparotomy from July 2021 to June 2023 in the Third Department of General Surgery of the People’s Hospital of Zhongshan City and Department of Surgery, the People’s Hospital of Gongbo’gyamda County, Xizang Autonomous Region were divided into the drainage tube group and the control group by whether staying a subcutaneous drainage tube or not in the surgery. The following data were observed and retrospectively analyzed of the incision recovery condition, the perioperative and follow-up clinical data.
Results
There were no significant differences in baseline clinical data between the two groups. The drainage tube group was superior to the control group in terms of primary incisional healing rate (χ2=5.221, P=0.035), 14 days incisional healing rate (χ2=5.082, P=0.032), incisional healing time (t=2.917, P=0.040) and suture removal time (t=3.279, P<0.001). While in terms of incisional fat liquefaction/seepage (χ2=12.443, P<0.001), incisional infection rate (χ2=5.347, P=0.025) and secondary suture rate (χ2=4.674, P=0.036), it was lower than the control group, and the patients’hospitalization satisfaction was improved (t=5.221, P=0.045). The differences between the two groups were statistically significant.
Conclusion
The subcutaneous drainage tube can effectively prevent the incisional infection after emergency laparotomy in obese patients, which is worthy of clinical promotion and application.
To investigate the relationship between serum tumor markers and colorectal cancer liver metastasis (CRLM), thus to establish a prediction model for CRLM and evaluate its application value.
Methods
A total of 371 patients with colorectal cancer admitted to Cangzhou Central Hospital from April 2021 to October 2022 were included in this study. They were divided into two groups according to whether there were liver metastases. There were 59 patients in the CRLM group and 312 patients in the non-CRLM group. Clinical data, test results of pre-treatment blood and serum tumor markers of patients were collected retrospectively. Binary Logistic regression was used to analyze the independent influencing factors of CRLM, and the diagnostic efficacy of the prediction model was evaluated using receiver operating characteristics (ROC) curve and goodness-of-fit test.
Results
Compared with non-CRLM group, neutrophil to lymphocyte ratio (NLR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and sialic acid/hydroxyproline (SA&Hyp) levels were significantly higher (all P<0.01). Binary Logistic regression analysis showed that the high levels of serum CEA (OR=1.021, 95% CI: 1.012-1.030), CA19-9 (OR=1.003, 95% CI: 1.001-1.005) and SA&Hyp (OR=1.055, 95% CI: 1.033-1.077) were independent risk factors for CRLM after correction (all P<0.01). ROC curve analysis revealed that the predictive modeling (AUC=0.867, 95% CI: 0.818-0.916, sensitivity was 0.831, specificity was 0.785) jointly constructed by CEA, CA19-9 and SA&Hyp was more effective in predicting CRLM compared with any single indicator (all P<0.05). The goodness-of-fit test results indicated that the prediction model had good matching (χ2=8.441, P=0.392).
Conclusions
High levels of serum CEA, CA19-9 and SA&Hyp are independent risk factors for CRLM. The prediction model of CRLM based on the joint detection of risk factors shows a reasonable predictive value and may provide new insights for the early diagnosis of CRLM in clinical work.
To construct a nomogram prediction model for early prediction of mortality risk in patients with non-mild acute pancreatitis (NMAP) and analyze its clinical application effect and advantages over other scoring systems.
Methods
Clinical data of 606 patients with NMAP from the large medical information mart for intensive careⅢ database (MIMIC-Ⅲ ) were selected. The patients were randomly divided into training and validation sets in a 7∶3 ratio. LASSO-Cox regression analysis was performed to construct a nomogram prediction model for mortality risk in NMAP patients. The model’s performance was assessed through receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Additionally, the predictive efficacy of the nomogram model was compared with BISAP, SOFA, qSOFA, APS Ⅲ, and OASIS scores.
Results
LASSO-Cox regression analysis identified age, systolic blood pressure within 24 hours of admission, red blood cell distribution width (RDW), serum albumin, blood urea nitrogen (BUN), total bilirubin, and international normalized ratio (INR) as independent risk factors associated with mortality in NMAP patients (P<0.05). A nomogram prognostic model was developed based on these factors. The area under the curve (AUC) for the nomogram model was 0.76 (95% CI: 0.67-0.83), 0.79 (95% CI: 0.72-0.83), 0.83 (95% CI: 0.77-0.87), and 0.83 (95% CI: 0.78-0.88), respectively, for predicting mortality at 14, 30, 60, and 90 days in NMAP patients. The validation set demonstrated AUC values of 0.85 (95% CI: 0.76-0.94), 0.83 (95% CI: 0.76-0.91), 0.86 (95% CI: 0.79-0.93), and 0.87 (95% CI: 0.81-0.93), respectively. Calibration curves indicated excellent agreement between predicted and observed probabilities of mortality in both the training and validation sets. The DCA curve indicated that the nomogram had significantly positive net benefit when the threshold probability ranged from approximately 0.2 to 0.8. The ROC curve revealed superior prediction efficiency of the nomogram model compared to BISAP, SOFA, qSOFA, APSⅢ, and OASIS scores (P<0.05).
Conclusion
The nomogram model, incorporating age, systolic blood pressure within 24 hours of admission, RDW, serum albumin, BUN, total bilirubin, and INR offers a simple and convenient tool for accurate prediction of death risk in NMAP patients early.
To investigate the effect of cisplatin on the expression of programmed death ligand 1 (PD-L1) in hepatocellular carcinoma Hep3B cells and the effect of PD-L1 on cisplatin sensitivity.
Methods
Hep3B cells were treated with 0, 5, 10, 20 mg/L cisplatin, and the expression of PD-L1 was detected by qPCR and Western blotting. Hep3B cells were treated in control group (PBS only), cisplatin group (5 mg/L), MK2206 group (AKT inhibitor, 5 μmol/L) and cisplatin+MK2206 group (5 μmol/L MK2206 was administered 1 hour before cisplatin treatment), and the expressions of AKT, p-AKT and PD-L1 were detected by Western blotting. siRNA-PD-L1 was transfected into Hep3B cells. Western blotting was used to detect the expression of PD-L1 and epithelial-mesenchymal transition markers (E-cadherin and N-cadherin). CCK-8, scratch assay and Transwell test were used to detect the changes of cell function.
Results
Cisplatin could up-regulate the protein level of PD-L1 in Hep3B cells (P<0.05). Compared with the control group, 5 mg/L cisplatin significantly increased the mRNA level of PD-L1 in Hep3B cells (P<0.05). MK2206 could attenuate the promoting effect of cisplatin on p-AKT and PD-L1 expression in Hep3B cells (P<0.05). There was no significant difference in the protein level of AKT. siRNA-PD-L1 could attenuate the promoting effect of cisplatin on PD-L1 expression in Hep3B cells (P<0.05), enhance the inhibitory effect of cisplatin on proliferation, migration and invasion of Hep3B cells, enhance the promoting effect of cisplatin on E-cadherin expression and the inhibitory effect of cisplatin on N-cadherin expression in Hep3B cells (P<0.05).
Conclusions
Cisplatin can promote the expression of PD-L1 in hepatocellular carcinoma Hep3B cells, and its mechanism may be related to the up-regulation of phosphorylation level of AKT pathway proteins. Inhibition of PD-L1 expression may enhance the sensitivity of Hep3B cells to cisplatin.
So far, the pathogenesis of gastric cancer (GC) has not been fully understood. Research shows that tumor microenvironment (TME) is essential for the occurrence and development of tumors. Tumor associated neutrophils (TANs) in TME are involved in all stages of tumor progression, including tumor initiation, metastasis, and immunosuppression. Due to the complex mechanism of TANs, the treatment of GC faces great challenges. With in-depth research on TME, specific treatment measures are expected for clinical treatment of GC. This article intends to review the literature in recent years, study and summarize the role of TANs in the occurrence and metastasis of GC, and briefly describe the development direction of targeted therapy in the future, trying to provide reference for clinical and scientific research.
The protein encoded by TCN1 is an important binding protein in the transport of serum vitamin B12, the expression levels of which affect DNA synthesis through the regulation of plasma vitamin B12 levels and thus contribute to the development of related diseases. Recent studies and bioinformatics analysis have shown that TCN1 plays an oncogene role in tumor tissues. TCN1 is involved in the adhesion, migration, proliferation, invasion and other biological behaviors of digestive tract tumor cells by regulating cancer transcriptional dysregulation pathway, NF-κB pathway, TNF signaling pathway, MAPK pathway, and affecting the activities of integrin β4 (ITGB4), pyruvate dehydrogenase complex (PDHA1), succinate dehydrogenase (SDH) and cytochrome c oxidase. Therefore, understanding the mechanism of TCN1 genes in gastrointestinal tumors is important for clinical diagnosis and therapeutic strategy.
Gastrointestinal stromal tumors (GISTs) are common malignant tumors of mesenchymal origin, originating from Cajal interstitial cells in the gastrointestinal tract. The three main molecular subtypes of GISTs are KIT mutant, platelet-derived growth factor receptor α (PDGFRA) mutant and wild type. Most GISTs have functional acquisition mutation of KIT or PDGFRA. Specific mutations limit well-defined molecular subtypes of GIST that should be determined during diagnosis to guide clinical management and treatment decisions. Surgery is an effective method for local GIST. At present, tyrosine kinase inhibitor (TKI) imatinib has been used as standard first-line treatment for metastatic GIST. Although the clinical benefit rate is 80%, most GIST patients have developed disease progression after 2-3 years of imatinib treatment. Second-line and third-line options include sunitinib and regofenil, respectively. Recently, the US Federal and Drug Administration has approved two new TKIs for the treatment of advanced/unresectable GISTs with severe pretreatment, including avatinib (selective inhibitor of Exon 18 mutation of PDGFRA, such as D842V mutation) and ripretinib (broad-spectrum kinase inhibitor of c-Kit and PDGFRA). The combination of targeted drugs and surgery can improve the prognosis of GISTs patients.
Suprapubic incisional hernia (SIH) is a special type of abdominal wall incision hernia, which specifically refers to incision hernia that occurs within 4 cm from the midline to the pubic arch. The hernia ring is adjacent to the bone, blood vessels, nerves and bladder and other structures. Because the posterior sheath of the rectus abdominis muscle is missing, surgical treatment is very challenging, and the selection of appropriate surgical methods has been controversial. The purpose of this article is to discuss the selection of surgical options for SIH, including indications for surgery, surgical methods, and prevention and treatment of complications. Traditional open surgery is still widely used, and laparoscopic surgery has been rapidly developing, with a variety of novel surgical procedures emerging. The differences between the various surgical procedures lie in the different surgical accesses and the different levels of placement of the repair material; the combination of open and laparoscopic procedures is a flexible option. In the process of abdominal wall reconstruction, the surgeons not only need to fully understand the complex anatomical structure and spatial anatomical relationship of the abdominal wall, but also have the ability to suture in the narrow space. The choice of surgical procedures should be based on an individualized plan, thorough evaluation of the patients’ general condition, combination of experiences, technical feasibility, economic accessibility of materials, and the overall financial burden.
Changiocarcinoma, insidious and highly malignant, is usually at the advanced stage when it is found out, and patients have lost the chance of radical surgical resection. For the palliative treatment of advanced cholangiocarcinoma, traditional methods include biliary stent placement, radiofrequency ablation, chemoradiotherapy and so on, but cholangiocarcinoma is not sensitive to chemoradiotherapy. In recent years, photodynamic therapy (PDT) has become another option for patients with advanced cholangiocarcinoma due to less trauma and adverse effects. It has been gradually applied to the palliative treatment of advanced cholangiocarcinoma and has achieved good results, thus attracts wide attention in the academic community. This paper summarizes the principles, advantages and disadvantages of the application of PDT for changiocarcinoma.
