The 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI) was held in San Francisco, the USA from January 18th to 20th, 2024 (local time). The multiple studies presented in this symposium will have a significant impact on the clinical practice of esophageal cancer. This article will focus on the surgical methods of esophageal cancer, perioperative immunotherapy, drug therapy for advanced esophageal cancer, rescue treatment after immunotherapy resistance, and other relevant aspects. It aims to summarize and interpret the significant advancements in the field of esophageal cancer presented in this symposium.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Objective:To study on the effects of gastrointestinal function and portal vein hemodynamics applicated with abdominal hot compressing with evodiae fructus and crude salt after hepatectomy.Methods:A total of 60 patients who underwent hepatectomy were randomly divided into 2 groups by random number table method, with 30 in each group. The control group was treated with conventional basic western medicine, while the treatment group was treated with medicinal evodiae fructus and crude salt hot compress on abdomen on the basis of the control group. The portal vein diameter (PVD), portal venous flow velocity (PVV), recovery time of main clinical indexes, clinical symptom scores and liver function indexes were dynamically monitored at different observation time points.Results:The scores of abdominal distension, nausea and vomiting in the treatment group were significantly lower than those in the control group 3 days after treatment ( t values were -3.489 and -2.740, respectively, all Ps<0.05). The recovery time of bowel sounds, first exhaust time and first defecation time in the treatment group were significantly earlier than those in the control group ( t values were -3.622, -4.297 and -4.151, respectively, all Ps<0.01). With the extension of treatment time, ALT in 2 groups showed a gradual downward trend ( P<0.05 or P<0.01), DBIL in control group was significantly higher at 3 days after treatment than before ( t=-2.157, P=0.039), and TBIL was significantly lower at 7 days after treatment than before ( t=2.175, P=0.038). The PVD ( t values were 3.528, 2.160) and PVV ( t values were 11.096, 4.264) of the treatment group were significantly higher than those of the control group 3 and 5 days after treatment ( P<0.01 or P<0.05). Conclusion:Early application of abdominal hot compressing with evodiae fructus and crude salt hot compress on abdomen after hepatectomy can improve the portal vein blood circulation and promote the rehabilitation of gastrointestinal function in patients with hepatectomy.

Objective:To identify the Key genes in the development of sepsis through weighted gene co-expression network analysis (WGCNA).Methods:The gene expression dataset GSE154918 was downloaded from the public database Gene Expression Omnibus (GEO) database, which containes data from 105 microarrays of 40 control cases, 12 cases of asymptomatic infection, 39 cases of sepsis, and 14 cases of follow-up sepsis. The R software was used to screen out differentially expressed genes (DEG) in sepsis, and the distributed access view integrated database (DAVID), search tool for retrieval of interacting neighbouring genes (STRING) and visualization software Cytoscape were used to perform gene function and pathway enrichment analysis, Protein-protein interaction (PPI) network analysis and key gene analysis to screen out the key genes in the development of sepsis.Results:Forty-six candidate genes were obtained by WGCNA and combined with DEG expression analysis, and these 46 genes were analyzed by gene ontology (GO) and Kyoto City Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to obtain gene functions and involved signaling pathways. The PPI network was further constructed using the STRING database, and 5 key genes were selected by the PPI network visualization software Cytoscape, including the mast cell expressed membrane protein 1 gene (MCEMP1), the S100 calcium-binding protein A12 gene (S100A12), the adipokine resistance factor gene (RETN), the c-type lectin structural domain family 4 member gene (CLEC4D), and peroxisome proliferator-activated receptor gene (PPARG), and differential expression analysis of each of these 5 genes showed that the expression levels of the above 5 genes were significantly upregulated in sepsis patients compared with healthy controls.Conclusion:In this study, 5 key genes related to sepsis were screened by constructing WGCNA method, which may be potential candidate targets related to sepsis diagnosis and treatment.

Objective:To investigate the value of programmed death-1（PD-1） expression on the T lymphocytes for the prognosis of septic patients.Methods:From September 2017 to May 2019, septic patients were included in Department of Intensive Care Unit at 6 hospitals. The PD-1 expression on T cells were measured by flow cytometry. Logistic regression was conducted to analyze independent risk factors related to death within 28 days，and receiver operating characteristic curve(ROC) was conducted to evaluate the prognostic value of PD-1 expression on T cells in septic patients.Results:A total of 64 septic patients were enrolled to this study，including 32 survivors and 32 deaths. The PD-1 expression on T cells in the death group was significantly higher than that in the surviving group ( P<0.05). Correlation analysis showed that the percentages of PD-1 +/CD3 +T cells and PD-1 +/CD8 +T cells were positively correlated with procalciton in ( r=0.313, P =0.015； r=0.375, P=0.003), logistic regression analysis showed that the percentages of PD-1 +/CD3 +，PD-1 +/CD4 +，PD-1 +/CD8 +T cells were independent risk factors for the death of sepsis patients. The percentage of PD-1 +/CD3 +T cell was 3.63%, with AUC 0.842, sensitivity to predict the mortality 96.43% and specificity 59.38%, ( P<0.000 1). The percentage of PD-1 +/CD4 +T cell was 4.65%, with AUC 0.847, sensitivity 96.43%, specificity 62.50%，( P<0.000 1). The percentage of PD-1 +/CD8 +T cell was 3.91%, with AUC 0.771, sensitivity 64.29%, specificity 81.25%，( P=0.000 3). Conclusions:The T cell PD-1 expression is an independent risk factor to predict the 28-day mortality in septic patients. Combining the proportions of PD-1 +/CD3 +, PD-1 +/CD4 +and PD-1 +/CD8 +T cells may further enhance the predictive value for death.

Objective To investigate the effect of the endoscopic surveillance system in irrigating fluid absorption and bleeding during transurethral resection of the prostate.Methods In vitro trials,we simulated the fluid absorption and bleeding in the operation by using self-developed endoscopic surveillance system from January 2013 to June 2013.Continuous irrigation of 5 ％ mannitol solution,we extracted 5 times irrigating fluid (each time 100 ml and a total of 500 ml) in the process of irrigation and recorded absorption measurements of every time extraction rinses.At the same time,we dripped human whole blood 5 times(each time 5 ml and a total of 25 ml) in the process of irrigation and recorded the bleeding measurements.The above process was repeated three times to detect the accuracy and consistency of the endoscopic surveillance system.In clinical trials,50 cases of BPH were monitored in surgery and the biochemical index,hemodynamics,irrigating fluid absorption and bleeding were compared from October 2016 to April 2017.The included criteria contained as follow:the age of patients should be more than 50 years.The transabdominal ultrasound showed that the volume of prostate should be more than 60 ml.The maximal uroflowmetry should be less than 15ml/s.The IPSS scores should be more than 8.Based on the operative time,two groups (＜60 min and ≥ 60 min) were classified.Results We developed the endoscopic surveillance system which is original in the world.In vitro trials,the average irrigating fluid were (100.60 ± 2.07) ml,(201.00±3.39) ml,(302.00±4.67) ml,(403.60±4.39) ml and (502.40 ±7.57) ml;and the average bleeding were (5.06 ± 0.11) ml,(10.10 ± 0.16) ml,(15.04 ± 0.15) ml,(20.06 ± 0.11) ml and (25.10 ± 0.16) ml.No significant difference was observed in all groups (P ＞ 0.05).In clinical trials,we compared some preoperative and postoperative indexes.The average blood oxygen saturation were (94.46 ± 2.49) ％ and (92.39 ± 2.77) ％ (P ＜ 0.01),the average Serum sodium ion concentration were (141.05 ± 2.52) mmol/L and (138.06 ± 4.27) mmol/L(P ＜ 0.01),the average HGB were (143.50 ± 13.43) g/L and (137.04 ± 14.25) g/L(P ＜ 0.01).The average HCT were (42.05 ± 4.09) ％ and (137.04 ± 14.25) ％ (P ＜ 0.01).The average HR were (77.9 ± 7.6) beats per minute and (77.93 ± 6.93) beats per minute (P＞0.05).The MAP were (90.32 ± 9.75) mmHg and (91.07±8.96)mmHg(P＞0.05).The average serum potassium ion concentration were (4.13 ± 0.53) mmol/L and (4.09 ± 0.37) mmol/L (P ＞ 0.05).The average irrigating fluid absorption of the group less than 60 minutes and the group equal or more than 60 minutes were (401.83 ± 279.23) ml and (885.25 ± 367.68) ml (P ＜ 0.01).The average blood loss were (64.10 ±47.47) ml and (158.40 ± 65.22) ml(P ＜0.01).The preoperative and postoperative hemodynamic,blood biochemical and hematology showed difference in our trials.Irrigating fluid absorption and blood loss were positively associated with operation time.Conclusions The endoscopic surveillance system was safety and accuracy.It can offer real-time monitoring data and alarm mechanism for the surgeons that possibly improve operation safety.

Objective To study the clinical features, diagnosis and treatment of torsion of testes in newborn. Method Neonates who were diagnosed with neonatal testicular torsion and admitted to Shenzhen Children's Hospital from March 2008 to July 2018 were studied. The clinical data such as days in age, time of onset, clinical manifestations, time of ultrasound examination, characteristics of ultrasound examination, surgery time, surgical types, postoperative conditions, pathological findings, and follow-up results were retrospectively analyzed. Result A total of 12 infants with torsion of testes were enrolled. The average onset time was 2.9 d, ranged from 1～10 d. The time of onset was within 24 h after birth in six infants. The median duration from onset to seeing a doctor was 3.5 d, ranged from 2 h to 28 d. First manifestations being reported grammer were scrotal swelling or mass, including 7 cases on the left side and 5 cases on the right side. Among them, 9 cases were associated with redness or cyanosis of the scrotum. Ultrasound was characterized by the disappearance or significant reduction of testicular parenchymal blood flow signal, and the sensitivity of ultrasound was 100％. The average time from admission to operation was (2.1±1.1) h. All the 12 infants had orchiectomy,after necrosis of unilateral testicle was confirmed. Eight of them underwent contralateral test icular fixation. The average operation time was 46 min. There was no wound bleeding or infection postoperatively, and the average hospital stay was 6.4 d. The pathological features were blurred residual contour of the seminiferous tubule (9 cases) or the disappearance of the seminiferous tubule structure (3 cases). After 3 to 24 months of follow-up, no contralateral testicular torsion or atrophy was found. Conclusion The rate of testicular necrosis in children with torsion of testes is high. The newborn with scrotal swelling should be diagnosed promptly with color Doppler ultrasound. If necessary, surgical exploration should be performed in time.

Objective To summarize and analyze the clinical features,diagnostic methods and treatment measures of patients with advanced spontaneous esophageal rupture. Methods Retrospective analysis of clinical characteristics of 10 patients with advanced spontaneous esophageal rupture was conducted. Results The average age of the patients was 49. 3 years old. The average time of diagnosis was 82. 6 hours. The cause of onset was drastic vomiting except for one case falling down. The main clinical manifestations were chest pain,abdominal pain,and shortness of breath,fever and elevation of hemogram,pleural effusion appeared in all patients,1 case was not treated in time,and 9 cases of the first checks were delayed for diagnosis and treatment in other specialties. Conservative treatment(closed thoracic drainage,gastrointestinal decompression,enteral nutrition support and antimicrobial therapy) was given to all patients. All 10 cases were cured by conservative treatment,the average time of hospitalization was 49. 4 days,followed up for 2 years, no chronic empyema, stricture of the esophagus and reflux esophagitis were observed. Conclusion Late spontaneous rupture of the esophagus is caused by delays in the diagnosis and treatment of the esophagus,the effect of comprehensive conservative treatment is satisfactory.

Objective To explore the impact of arterial injury on distal limb blood supply in lower limb trauma. Meth?ods Retrospective analysis of 93 patients with different levels of lower limb arterial injury admitted to our hospital from June 2014 to August 2017. There were 84 males and 9 females aged 43.54±9.90 years (ranging 25-65 years). Revascularization was performed through open reduction. Patients were divided into three groups according to their arterial injury locations. Proximal ves?sels were along the superficial femoral artery, from its beginning to the point where it was divided into the descending genicular ar?tery and direct periosteal branches. Intermediate vessels were from the dividing point on the superficial femoral artery to the popli?teal artery before it was divided into the medial inferior genicular artery. Distal vessels were from the dividing point on the poplite?al artery to the distal end of the peroneal artery. The duration from injury to revascularization in the three groups were 13.67±5.99 h, 11.15±4.43 h, and 11.92±5.48 h, respectively. There was no significant difference between groups (F=1.564, P=0.215). ISS in the three groups were 13.00±3.74, 12.77±3.81, and 11.50±3.99, respectively. There was no significant difference between groups (F=1.445, P=0.241). The following items were compared among the three groups, postoperative creatine kinase, arterial blood lac?tate and limb compartment cut. Results Creatine kinase of the intermediate vascular group was 8 743.15±6 968.48 u/L, proximal vascular group 1 467.67±1 810.27 u/L, distal vascular group 2 893.51±1 304.56 u/L. The data of intermediate vascular group were higher than those of proximal and distal vascular groups with significant difference among the groups (F=22.587,P=0.000). The lactate of the intermediate vascular group was 3.20 ± 1.51 mmol/L, proximal vascular group 1.63 ± 0.46 mmol/L, distal vascular group 1.85±0.69 mmol/L with significant difference among the groups (F=20.612,P=0.000). The compartment cut of the intermedi?ate vascular group was incised in 24, but not in 15. The proximal vascular group was not incised in 18, while 15 was incised and 21 not incised in distal vascular group. The rates of compartment cut were 61.5%, 0 and 41.7%, respectively with significant differ? ences (χ2=19.156, P=0.000). Conclusion In lower limb injuries, the intermediate vascular (from the superficial femoral artery after it is divided into the descending genicular artery and direct periosteal branches to the popliteal artery before it is divided into the medial inferior genicular artery) injury leads to the most severe distal limb ischemia.

Sepsis is a common disease in critical patients, which may lead to myocardial damage, thereby aggravating the severity of the patients' condition, and causing adverse prognosis. How to detect sepsis with myocardial injury as early as possible, and use corresponding treatment measures on time are essential. Cardiac troponin I (cTnI), brain natriuretic peptide (BNP), myoglobin (Mb), MB isoenzyme of creatine kinase (CK-MB) and other traditional cardiac markers are easily affected by the complications of other critical diseases, thus the diagnostic value of those markers for myocardial injury of sepsis is reduced. In recent years, there have been some studies on heart-type fatty acid binding protein (H-FABP), microRNA (miRNA), soluble triggering receptor expressed on myeloid cell-1 (sTREM-1), high mobility group protein B1 (HMGB1), neutrophil gelatinase-associated lipocalin (NGAL), histone and other new biomarkers of myocardial injury in septic patients. This article reviewed the value of these unconventional cardiac markers in the diagnosis of sepsis-induced myocardial injury, with the hope to provide some help for clinic.