Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC.Methods:In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging.Results:Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ 2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ 2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion:Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.

Objective:To compare the short-term efficacy of laparoscopic sleeve gastrectomy (LSG) combined with sharp His angle reconstruction (LSG-His) versus traditional LSG.Methods:In this retrospective cohort study we collected clinical data of patients with obesity who had undergone LSG or LSG-His in the Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, from January to June 2022. After excluding patients with incomplete follow-up data and those with hiatal hernia, 83 obese patients, of which 39 who had undergone LSG (LSG group) and 44 who had undergone LSG-His (LSG-His group), were included in the study. The basic steps in LSG-His are the same as in conventional LSG. After continuous suturing of the gastric staple line, one stitch is placed between the proximal side of the gastric greater curvature staple line and the proximal side of the gastric fundus posterior wall with the left diaphragm, and another stitch between the right side of the gastric fundus and the esophagus, reconstructing the sharp His angle. Clinical data, postoperative complications, and follow-up data on weight loss and gastroesophageal reflux disease (GERD) symptoms 1-, 3-, 6-, and 12-months post-discharge were compared between the two groups. GERD symptoms were assessed using the Gastroesophageal Reflux Disease Questionnaire and Reflux Diagnostic Questionnaire.Results:There were no significant differences between the two groups in baseline characteristics, length of hospital stay, hospitalization costs, intraoperative bleeding, postoperative nausea and vomiting, dysphagia, or postoperative complications (all P>0.05). Compared with the LSG group, the LSG-His group had significantly longer operative times (92 [80, 100] minutes vs. 80 [70, 100] minutes, U=2.227, P=0.026), higher postoperative 24-hour pain scores (5.2±1.8 vs. 4.3±1.9, t=-2.065, P=0.041), and higher rates of morphine use (70.5% [31/44] vs. 46.2% [18/39], χ2=4.519, P=0.025). The incidence of new-onset GERD 12 months postoperatively was significantly lower in the LSG-His than the LSG group (10.7% [3/28] vs. 61.3% [19/31], χ2=14.00, P<0.001). According to changes in Gastroesophageal Reflux Disease Questionnaire and Reflux Diagnostic Questionnaire scores, the LSG-His group also had significantly lower rates of exacerbation of GERD (2/16 vs. 5/8, χ2=4.27, P=0.021) and higher rates of GERD remission (12/16 vs. 2/8, χ2=3.62, P=0.032) than did the LSG group. Additionally, excess weight loss rates were significantly higher in the LSG-His group at 3 months [(54.7± 18.7)% vs. (46.5±15.0)% , t=-2.166, P=0.033], 6 months [(73.8±24.7)% vs. (64.0±19.1)% , t=-2.018, P=0.047], and 12 months [(82.9±26.7)% vs. (72.2±19.3)%, t=-2.063, P=0.042] than in the LSG group. Conclusion:Compared with LSG, LSG-His is safe and feasible and achieves better short-term control of postoperative GERD and more effective weight loss. Further large-scale, long-term, prospective studies are needed to confirm the long-term efficacy of LSG-His.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC.Methods:In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging.Results:Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ 2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ 2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion:Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.

Objective:To compare the short-term efficacy of laparoscopic sleeve gastrectomy (LSG) combined with sharp His angle reconstruction (LSG-His) versus traditional LSG.Methods:In this retrospective cohort study we collected clinical data of patients with obesity who had undergone LSG or LSG-His in the Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, from January to June 2022. After excluding patients with incomplete follow-up data and those with hiatal hernia, 83 obese patients, of which 39 who had undergone LSG (LSG group) and 44 who had undergone LSG-His (LSG-His group), were included in the study. The basic steps in LSG-His are the same as in conventional LSG. After continuous suturing of the gastric staple line, one stitch is placed between the proximal side of the gastric greater curvature staple line and the proximal side of the gastric fundus posterior wall with the left diaphragm, and another stitch between the right side of the gastric fundus and the esophagus, reconstructing the sharp His angle. Clinical data, postoperative complications, and follow-up data on weight loss and gastroesophageal reflux disease (GERD) symptoms 1-, 3-, 6-, and 12-months post-discharge were compared between the two groups. GERD symptoms were assessed using the Gastroesophageal Reflux Disease Questionnaire and Reflux Diagnostic Questionnaire.Results:There were no significant differences between the two groups in baseline characteristics, length of hospital stay, hospitalization costs, intraoperative bleeding, postoperative nausea and vomiting, dysphagia, or postoperative complications (all P>0.05). Compared with the LSG group, the LSG-His group had significantly longer operative times (92 [80, 100] minutes vs. 80 [70, 100] minutes, U=2.227, P=0.026), higher postoperative 24-hour pain scores (5.2±1.8 vs. 4.3±1.9, t=-2.065, P=0.041), and higher rates of morphine use (70.5% [31/44] vs. 46.2% [18/39], χ2=4.519, P=0.025). The incidence of new-onset GERD 12 months postoperatively was significantly lower in the LSG-His than the LSG group (10.7% [3/28] vs. 61.3% [19/31], χ2=14.00, P<0.001). According to changes in Gastroesophageal Reflux Disease Questionnaire and Reflux Diagnostic Questionnaire scores, the LSG-His group also had significantly lower rates of exacerbation of GERD (2/16 vs. 5/8, χ2=4.27, P=0.021) and higher rates of GERD remission (12/16 vs. 2/8, χ2=3.62, P=0.032) than did the LSG group. Additionally, excess weight loss rates were significantly higher in the LSG-His group at 3 months [(54.7± 18.7)% vs. (46.5±15.0)% , t=-2.166, P=0.033], 6 months [(73.8±24.7)% vs. (64.0±19.1)% , t=-2.018, P=0.047], and 12 months [(82.9±26.7)% vs. (72.2±19.3)%, t=-2.063, P=0.042] than in the LSG group. Conclusion:Compared with LSG, LSG-His is safe and feasible and achieves better short-term control of postoperative GERD and more effective weight loss. Further large-scale, long-term, prospective studies are needed to confirm the long-term efficacy of LSG-His.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Colorectal cancer (CRC) is one of the most common digestive system tumors and the second most common tumor in the world in terms of mortality. The current chemotherapeutic drugs applied in clinical treatment seriously affect the survival quality of patients due to adverse reaction and susceptibility to chemoresistance. Therefore, it is necessary to search for novel anti-CRC drugs. As natural compounds, polyphenols components of traditional Chinese medicine can exert anti-CRC properties through various mechanisms, such as promoting apoptosis, inhibiting cell proliferation, and inducing iron death. In addition, it can reverse the resistance of CRC cells to chemotherapeutic drugs. Further exploration of the anti-CRC action mechanism of polyphenols constituents of traditional Chinese medicine may provide a certain reference basis for clinical application.

Objective:To investigate the correlation of CD8 positive tumor-infiltrating lymphocytes (CD8 + TIL) density and programmed-death receptor ligand 1 (PD-L1) expression in rectal cancer with clinicopathological characteristics and prognosis of patients after neoadjuvant chemoradiotherapy. Methods:The clinicopathological data of 166 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgery in the Beijing Chao-Yang Hospital, Capital Medical University from January 2015 to December 2018 were retrospectively analyzed. CD8 + TIL density and PD-L1 expression were detected by using immunohistochemistry. The correlation of CD8 + TIL density and PD-L1 expression with clinicopathological characteristics of patients after neoadjuvant chemoradiotherapy was analyzed. Kaplan-Meier method was used to analyze the disease-free survival (DFS) and Cox regression risk model was used to make univariate and multivariate analysis of the influencing factors for DFS. Results:Among 166 LARC patients, 81 cases (48.8%) had high density of CD8 + TIL, 85 cases (51.2%) had low density of CD8 + TIL; 63 cases (38.0%) had PD-L1 expression, and 103 cases (62.0%) had non-expression of CD8 + TIL. The expression rate of PD-L1 in CD8 + TIL high density group was higher than that in CD8 + TIL low density group [50.6% (41/81) vs. 25.9%(22/85), χ2 = 10.78, P < 0.001]. According to the density of CD8 + TIL and PD-L1 expression, immunophenotype was divided among 4 groups; the 3-year DFS rate of the CD8 + TIL high density /PD-L1 expression group was 87.1%, which was higher than that of the other groups (CD8 + TIL low density /PD-L1 expression group was 72.8%, CD8 + TIL high density /PD-L1 non-expression group was 67.0%, CD8 + TIL low density /PD-L1 non-expression group was 64.3%), and the difference was statistically significant ( P < 0.05). Univariate analysis showed that tumor differentiation degree, TNM stage, CD8 + TIL density, PD-L1 expression and CD8 + TIL density /PD-L1 expression were correlated with the DFS of patients (all P < 0.05). Multivariate analysis results showed that CD8 + TIL high density /PD-L1 expression was an independent protective factor for DFS ( HR = 0.049, 95% CI 0.005-0.497, P = 0.011), while TNM stage 3 was an independent risk factor for DFS ( HR = 2.752,95% CI 1.300-5.825, P = 0.008). Conclusions:In LARC after neoadjuvant therapy, CD8 + TIL density is positively correlated with the expression of PD-L1, and the high density of CD8 + TIL/PD-L1 expression is an independent influencing factor for good prognosis, suggesting that these patients may benefit from the immunotherapy.