Objective:To construct and validate a predictive model for pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy.Methods:This retrospective observational study included 595 patients with stage T2-4 and (or) N+M0 LARC diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences and the Fourth Hospital of Hebei Medical University who had no metastases, tolerated neoadjuvant therapy, completed neoadjuvant therapy, and had undergone radical surgery after neoadjuvant therapy. The training set comprised 299 patients admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 2013 to 2018, the internal validation set 155 patients admitted from 2019 to 2023, and the external validation set 141 patients admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2021. They were divided into pCR group and non-pCR groups according to postoperative pathology. Among the 299 patients in the training set, 247 were in the non-PCR and 52 in the pCR group; among the 155 patients verified internally, 113 were in the non-PCR and 42 in the pCR group; and among the 141 patients validated externally, 132 were in the non-pCR and nine in the pCR group. Logistic regression was used for univariate and multifactorial analysis to explore the factors associated with pCR and construct a nomogram prediction model. Receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to validate the performance of the predictive model.Results:Univariate and multivariate logistic regression analysis showed that carbohydrate antigen 19-9 ( P=0.040, OR=0.97, 95%CI: 0.93-0.99), neutrophil count ( P<0.001, OR=0.66, 95%CI: 0.52-0.84), tumor T stage: Stage IV ( P=0.011, OR=0.22, 95%CI: 0.07-0.70), tumor N stage: Stage I ( P=0.003, OR=0.22,95%CI:0.08-0.60), Stage II ( P<0.001, OR=0.03, 95%CI: 0.01-0.09) and involvement of mesorectal fascia ( P=0.004, OR=0.09, 95%CI: 0.02-0.47) were independent predictors of pCR. In the training set, the area under the receiver operating characteristic curve of the model was 0.92 (95%CI: 0.87-0.96), whereas in the internal and external validation sets, the AUCs were 0.78 and 0.81, respectively. The calibration curve showed that the prediction model had good prediction efficiency in both the training and verification sets. Decision curve analysis showed that the net benefit of the model was largest when the threshold probability was in the range of 5.2% to 89.7% (in the internal and external validation sets, the threshold probabilities were in the range of 15.7% to 92.3% and 2.2% to 84.1%, respectively). Conclusion:The nomogram model constructed in this study showed efficacy in predicting whether patients with LARC will achieve pCR after receiving neoadjuvant chemoradiotherapy.

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To explore the safety and efficacy of laparoscopic-assisted radical surgery in the treatment of metachronous multiple primary colorectal cancer (MCC).Methods:A retrospective analysis was conducted on 27 MCC patients undergoing laparoscopic-assisted radical surgery (laparoscopic group) and 36 MCC patients undergoing open radical surgery (open group) from Jan 2012 to Jan 2022 at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences.Results:The laparoscopic group was superior to the open group in terms of intraoperative blood loss [(53.7±111.5) ml vs. (132.5±154.9) ml, t=-2.241, P=0.029], time to first postoperative flatus [(2.2±0.7) days vs. (3.5±0.6) days, t=-7.752, P<0.001], time to first postoperative defecation [(2.9±0.6) days vs. (4.3±0.6) days, t=-8.841, P<0.001], and postoperative hospital stay [(7.2±2.4) days vs. (10.6±3.5) days, t=-4.518, P<0.001]. There were no significant differences between the two groups in terms of operation time, number of lymph nodes dissected, positive rate of specimen margin, resection rate of previous colorectal cancer anastomotic stoma, and incidence of postoperative complications (all P>0.05). Conclusion:Laparoscopic surgery is a safe and minimally invasive alternative to open surgery for MCC patients.

Objective:To construct and validate a predictive model for pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy.Methods:This retrospective observational study included 595 patients with stage T2-4 and (or) N+M0 LARC diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences and the Fourth Hospital of Hebei Medical University who had no metastases, tolerated neoadjuvant therapy, completed neoadjuvant therapy, and had undergone radical surgery after neoadjuvant therapy. The training set comprised 299 patients admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 2013 to 2018, the internal validation set 155 patients admitted from 2019 to 2023, and the external validation set 141 patients admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2021. They were divided into pCR group and non-pCR groups according to postoperative pathology. Among the 299 patients in the training set, 247 were in the non-PCR and 52 in the pCR group; among the 155 patients verified internally, 113 were in the non-PCR and 42 in the pCR group; and among the 141 patients validated externally, 132 were in the non-pCR and nine in the pCR group. Logistic regression was used for univariate and multifactorial analysis to explore the factors associated with pCR and construct a nomogram prediction model. Receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to validate the performance of the predictive model.Results:Univariate and multivariate logistic regression analysis showed that carbohydrate antigen 19-9 ( P=0.040, OR=0.97, 95%CI: 0.93-0.99), neutrophil count ( P<0.001, OR=0.66, 95%CI: 0.52-0.84), tumor T stage: Stage IV ( P=0.011, OR=0.22, 95%CI: 0.07-0.70), tumor N stage: Stage I ( P=0.003, OR=0.22,95%CI:0.08-0.60), Stage II ( P<0.001, OR=0.03, 95%CI: 0.01-0.09) and involvement of mesorectal fascia ( P=0.004, OR=0.09, 95%CI: 0.02-0.47) were independent predictors of pCR. In the training set, the area under the receiver operating characteristic curve of the model was 0.92 (95%CI: 0.87-0.96), whereas in the internal and external validation sets, the AUCs were 0.78 and 0.81, respectively. The calibration curve showed that the prediction model had good prediction efficiency in both the training and verification sets. Decision curve analysis showed that the net benefit of the model was largest when the threshold probability was in the range of 5.2% to 89.7% (in the internal and external validation sets, the threshold probabilities were in the range of 15.7% to 92.3% and 2.2% to 84.1%, respectively). Conclusion:The nomogram model constructed in this study showed efficacy in predicting whether patients with LARC will achieve pCR after receiving neoadjuvant chemoradiotherapy.

Objective:To explore the safety and efficacy of laparoscopic-assisted radical surgery in the treatment of metachronous multiple primary colorectal cancer (MCC).Methods:A retrospective analysis was conducted on 27 MCC patients undergoing laparoscopic-assisted radical surgery (laparoscopic group) and 36 MCC patients undergoing open radical surgery (open group) from Jan 2012 to Jan 2022 at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences.Results:The laparoscopic group was superior to the open group in terms of intraoperative blood loss [(53.7±111.5) ml vs. (132.5±154.9) ml, t=-2.241, P=0.029], time to first postoperative flatus [(2.2±0.7) days vs. (3.5±0.6) days, t=-7.752, P<0.001], time to first postoperative defecation [(2.9±0.6) days vs. (4.3±0.6) days, t=-8.841, P<0.001], and postoperative hospital stay [(7.2±2.4) days vs. (10.6±3.5) days, t=-4.518, P<0.001]. There were no significant differences between the two groups in terms of operation time, number of lymph nodes dissected, positive rate of specimen margin, resection rate of previous colorectal cancer anastomotic stoma, and incidence of postoperative complications (all P>0.05). Conclusion:Laparoscopic surgery is a safe and minimally invasive alternative to open surgery for MCC patients.

The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.

The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.

Objective To observe the value of vector flow mapping(VFM)technique for assessing changes of left ventricular diastolic function in ovarian cancer(OC)patients who underwent postoperative chemotherapy.Methods Totally 37 OC patients who received postoperative chemotherapy were prospectively enrolled in chemotherapy group,while 40 healthy adults were taken as controls(control group).Routine echocardiography and VFM were performed for chemotherapy group before chemotherapy,after 3 and 6 cycles of chemotherapy,also for controls at enrollment,and comparison was performed between groups before chemotherapy,as well as among different time points within chemotherapy group,and the correlations of VFM results with hemoglobin and routine echocardiographic results in chemotherapy group were analyzed.Results No significant difference of age,body mass,body surface area(BSA),nor hemoglobin level,routine echocardiographic and VFM results before chemotherapy was found between groups(all P＞0.05).With the process of chemotherapy,hemoglobin level gradually decreased,the isovolumic relaxation period(IR),atrial systole period(AS)intraventricular pressure difference(IVPD)and intraventricular pressure gradient(IVPG)of the left ventricle gradually increased(adjusted P＜0.05),whereas routine echocardiography only showed that the left atrial volume index(LAVI)and the ratio of early mitral inflow velocity and the mean mitral annular early diastolic velocity(E/e')increased after 6 cycles of chemotherapy compared with those pre-chemotherapy(adjusted P＜0.05).In chemotherapy group,VFM results in all diastolic subphases were strongly correlated with hemoglobin levels(|r|=0.718 to 0.836,all P＜0.05),weakly to moderately correlated with LAVI(|r|=0.375 to 0.525,all P＜0.05)and moderately correlated with E/e'(|r|=0.424 to 0.537,all P＜0.05).Conclusion The diastolic function of left ventricle was probably damaged in early stage after postoperative chemotherapy in OC patients.VFM might detect slight changes of early diastolic function of left ventricle more sensitively than routine echocardiography.

Objective:To investigate the impact of the clinicopathological characteristics of anorectal malignant melanoma (ARMM) on the prognosis.Methods:The clinicopathological data of 40 ARMM patients undergoing surgery at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from Apr 2012 to Apr 2022 were collected, and the impact of different clinicopathological factors and treatment modalities on the overall survival of ARMM patients was investigated using Kaplan-Meier survival analysis and multifactorial Cox proportional risk model analysis.Results:Among 40 ARMM patients , 16 were male and 24 were female. The median age of onset was 61 yr. The median follow-up period for all patients was 47 (25-69) months, with a median survival of 19 (15-23) months and 1-year and 3-year survival rates of 74.3% and 21.7%, respectively. There was no statistically significant difference in survival time between the two groups of patients receiving wide local excision and abdominoperineal resection( χ2=1.281, P=0.258). Univariate analysis showed that overall survival in patients with ARMM was related to tumour diameter, depth of infiltration, specimen margin and lymph node metastasis ( χ2=1.281, P=0.039; χ2=3.760, P=0.042; χ2=6.581, P=0.010; χ2=21.683, P<0.001), and multivariate analysis suggested that lymph node metastasis was an independent risk factor for overall survival in patients with ARMM. Conclusion:Tumour diameter, depth of infiltration, specimen margin and lymph node metastasis were important prognostic influences in ARMM, and lymph node metastasis was an independent risk factor for overall survival in ARMM patients.

Objective:To explore the application value of a novel ultrasonic scale in the evaluation of sub-massive pulmonary embolism (sub-PE).Methods:Retrospective analyses were conducted in 137 patients with acute pulmonary embolism confirmed by computed tomography pulmonary angiography (CTPA) in the second affiliated hospital of Harbin Medical University from September 2017 to June 2019. They were divided into experimental set (77 cases) and testing set(60 cases). According to the European Society of Cardiology (ESC) guidelines for pulmonary embolism in 2019, the patients were classified into sub-PE(71 cases) and small pulmonary embolism(small-PE, 66 cases). Parameters in the experimental set were screened by statistical methods to make an ultrasonic scale, and then the patients in the testing set were scored by the scale. ROC curve was plotted to calculate the diagnostic efficacy of the ultrasonic scale for sub-PE.Results:①The patients of sub-PE were older than small-PE patients [(61.57±1.45) years vs (56.31±1.59) years, P=0.016], but there was no significant difference between the two groups in other general data( P>0.05). ②Within the 77 pulmonary embolism patients in the experimental set, 41(53.25%) were classified as the sub-PE and 36(46.75%) as the small-PE. Compared with the small-PE group, right ventricular diameter, pulmonary artery trunk diameter, right ventricle/left ventricle ratio, tricuspid regurgitation velocity, the Tei index and the inferior vena cava diameter in the sub-PE group increased significantly ( P<0.05), and right ventricular wall motion amplitude, right atrium area rate, right ventricular area rate, tricuspid annulus systolic displacement, collapse rate of inferior vena cava and pulmonary artery blood flow acceleration time decreased significantly ( P<0.05); ③Fifteen ultrasonic parameters were used in the ultrasonic scale. The scale in sub-PE group of the testing set was significantly increased compared with that in small-PE group (11.63±3.87 vs 4.43±1.96, P<0.001). ROC showed that the AUC in diagnosing sub-PE by ultrasonic scale was 0.96. When the cut-off value was 6.5, the sensitivity and specificity were 90.00% and 83.33%, respectively. Conclusions:The novel ultrasonic scale can provide a comprehensive and feasible ultrasound imaging method for evaluation of sub-PE.