1.Osthole ameliorates chronic pruritus in 2,4-dichloronitrobenzene-induced atopic dermatitis by inhibiting IL-31 production.
Shuang HE ; Xiaoling LIANG ; Weixiong CHEN ; Yangji NIMA ; Yi LI ; Zihui GU ; Siyue LAI ; Fei ZHONG ; Caixiong QIU ; Yuying MO ; Jiajun TANG ; Guanyi WU
Chinese Herbal Medicines 2025;17(2):368-379
OBJECTIVE:
This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms.
METHODS:
In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated huma immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining.
RESULTS:
Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells.
CONCLUSION
These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.
2.An integrated prognostic model of nuclear-encoded mitochondrial gene signature and clinical information for hepatocellular carcinoma
Aishanjiang KEDEERYA ; Yi FU ; Donglin LAI ; Hailong WU ; Wei GONG
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(1):1-12
Objective·To establish a prognostic model for the overall survival(OS)of hepatocellular carcinoma(HCC)based on mitochondrial genes and clinical information.Methods·The gene expression and the clinical data of 369 HCC patients and 50 controls with normal liver were downloaded from The Cancer Genome Atlas(TCGA)database.The nuclear-encoded mitochondrial genes(NEMGs)were obtained from the MitoCarta3.0 database.The"DESeq2"R package and univariate Cox analysis were used to select NEMGs[ubiquinol cytochrome C reductase hinge protein(UQCRH),ATP citrate lyase(ACLY),phosphoenolpyruvate carboxykinase 2(PCK2),Bcl-2 homologous antagonist/killer1(BAK1),Bcl-2-associated X protein(BAX)and Bcl-2/adenovirus E1B interacting protein 3-like(BNIP3L)]in HCC that were associated with OS of HCC and participated in dysregulation of oxidative phosphorylation,tricarboxylic acid cycle and cell apoptosis.Multivariate Cox analysis was applied to select independent risk factors for OS of HCC.A comprehensive prognostic model and a prognostic nomogram with 6-NEMG risk characteristics and TNM staging were established.By using the median of prognostic scores as a cut-off,HCC patients were classified into low-risk and high-risk group.Kaplan-Meier survival curve analysis was conducted and log-rank test was performed to evaluate the survival rates between the low-risk and high-risk group.The area under the curve(AUC)values of receiver operating characteristic(ROC)curve were calculated via using the"timeROC"package.The prognostic model for HCC was validated by using the GEO HCC cohort(GSE14520)for 1,3 and 5 years.Finally,the relative expression level of 6-NEMG was validated in 34 clinical samples of HCC from Xinhua Hospital,Shanghai Jiao Tong University School of Medicine by using real-time quantitative polymerase chain reaction(qPCR)method.Results·Compared to 6-NEMG risk signature only(AUCs for 1,3 and 5 years were 0.77,0.66 and 0.65,respectively)or TNM stage only(AUCs for 1,3 and 5 years were 0.66,0.67 and 0.63,respectively),ROC curve analysis showed that this integrated prognostic model displayed better predictive performance for 1-year(AUC,0.78),3-year(AUC,0.73)and 5-year(AUC,0.69)OS of HCC.The Kaplan-Meier survival curve analysis showed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group(P=0.001).In addition,predictive performance of the prognostic model(AUC for 1,3 and 5 years is 0.67,0.66 and 0.74,respectively)and prognostic differences between the high-risk and low-risk group(P=0.001)were further validated in GEO(GSE14520)external cohort,and these results were consistent with the TCGA data.In addition to BNIP3L,dysregulation of five other NEMGs in the clinical HCC cohort was validated.The correlation analysis in GSE14520 and HCC clinical cohort showed a positive correlation between prognosis score and the size and number of tumors.Conclusion·A new prognostic model that combines 6-NEMG risk characteristics with TNM staging for predicting OS in HCC patients was constructed and validated.This model may help improve the prognosis prediction of HCC patients.
3.Effects of tumor location and mismatch repair on clinicopathological features and survival for non‐metastatic colon cancer: A retrospective, single center, cohort study
Zhen SUN ; Weixun ZHOU ; Kexuan LI ; Bin WU ; Guole LIN ; Huizhong QIU ; Beizhan NIU ; Xiyu SUN ; Junyang LU ; Lai XU ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2024;27(6):591-599
Objective:To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers.Methods:This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two‐thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left‐sided colon cancers (LCCs). Clinicopathological features were compared using the χ 2 test or Mann‐Whitney U test. Survival was estimated by Kaplan‐Meier curves and the log‐rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results:The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ 2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m 2 vs. 23.2 [21.3, 25.5] kg/m 2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ 2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ 2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ 2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow‐up time for all patients was 48 (range 33, 59) months. The log‐rank test revealed no significant differences in disease-free survival (DFS) ( P=0.668) or overall survival (OS) ( P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204?0.862, P=0.018), whereas a higher proportion of T3‐4 (HR=2.178, 95%CI: 1.089?4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443?3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115?3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146?0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103?1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log‐rank test revealed no significant differences in DFS ( P=0.343) or OS ( P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS ( P=0.047) and OS ( P=0.040) than did patients with pMMR. Conclusions:Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.
4.Impacts of participation in surgical clinical trial on safety and survival outcomes in patients with right-sided colon cancer
Huaqing ZHANG ; Guoqiang WANG ; Bin WU ; Guole LIN ; Huizhong QIU ; Beizhan NIU ; Junyang LU ; Lai XU ; Xiyu SUN ; Guannan ZHANG ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2024;27(9):928-937
Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.
5.Clinical characteristics and prognosis of brain metastasis in locally advanced rectal cancer
Ganbin LI ; Xiao ZHANG ; Chentong WANG ; Xiaoyuan QIU ; Guannan ZHANG ; Beizhan NIU ; Lai XU ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1063-1068
Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.
6.Risk analysis and control suggestions for suicidal abuse of over-the-counter drug difenidol tablets
Li ZUO ; Wen-Yu WU ; Hai-Qiang WU ; Yi-Hong LIN ; Shu-Kun LAI ; Bin WU ; Qian WANG
The Chinese Journal of Clinical Pharmacology 2024;40(8):1213-1216
Objective To analyze the literature related to diphenidol tablets poisoning,the characteristics of poisoning were summarized to provide reference for controlling the suicidal abuse risk of diphenidol tablets.Methods The global literature on suicide,overdose,poisoning,shock,and death related to difenidol published from January 1,2011 to December 31,2022 was analyzed,including gender,age,dosage,cardiac(blood)concentration,poisoning symptoms,etc.Results Young women were the majority of people with poisoning.The highest proportion of the age group is 11 to 30 years group.Patients who take medication doses greater than 3 000 mg may have a higher risk of death;patients with a heart(blood)concentration greater than 6 μg·mL-1 may have a higher risk of death.Malignant arrhythmia,consciousness disorders,coma,and apnea are common serious adverse events during poisoning.Conclusion It is recommended that the drug regulatory authorities should require the Listing permit holder of difenidol tablets to add the risk and symptoms of poisoning into the instructions.It is suggested that restricting individual consumers from purchasing large amounts of difenidol tablets in the short term.It is recommended that canceling the high-dose sales packaging of difenidol tablets.It is suggested that converting difenidol tablets into prescription drugs,even consider canceling the registration certificate of difenidol tablets.
7.Rivularin regulates the proliferation,apoptosis and metastasis of lung squamous cell carcinoma through LncRNA HOXA11-AS
Jian WU ; Yi-Lai SONG ; Zhong-Guo LIU
The Chinese Journal of Clinical Pharmacology 2024;40(20):3013-3017
Objective To investigate the molecular mechanisms by which Rivularin regulates the occurrence and metastasis of lung squamous cell carcinoma.Methods The relative expression levels of target genes in different cell lines were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Animal experiments:Animals were randomly divided into two groups,with the Rivularin animal group received 50 mg·kg-1 Rivularin solution daily by gavage;and the model group received an equal volume of 0.9%NaCl daily.Tumor volume was measured.Cell experiments:Cells were divided into control group(no treatment),scutellarin group(3.0 g·L-1 scutellarin),scutellarin+oe-HOXA11-AS group(3.0 g·L-1scutellarin extract treatment and transfection of HOXA11-AS),scutellarin+oe-HOXA11-AS+XAV939 group(3.0 g·L-1 scutellarin extract treatment,transfection of HOXA11-AS and addition of 10 μmol·L-1 XAV939).5-ethynyl-2'-deoxyuridine(Edu)and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assays were used to detect the proliferation and apoptosis rates of cells,respectively;the Transwell assay was used to detect the migration number of NCI-H520 cells in each group.Results The relative expression levels of HOXA11-AS in each lung cancer cell line were significantly higher than those in normal lung epithelial cells(all P<0.05).At 35 days,the tumor volumes of the model group and Rivularin animal group were(937.83±67.40)and(512.32±45.61)mm3,respectively;compared between two groups,the difference was statistically significant(P<0.001).The number of cell migration in the control group,Rivularin group,Rivularin+oe-HOXA11-AS group,and Rivularin+oe-HOXA11-AS+XAV939 group were 127.26±8.92,23.76±3.31,131.28±9.49 and 27.69±3.57;the proliferation rates were(56.27±7.49)%,(28.68±4.33)%,(50.12±7.86)%and(13.62±3.54)%respectively;the apoptosis rates were(10.86±2.97)%,(43.23±6.78)%,(30.92±4.53)%and(41.77±7.02)%.The above indicators of the Rivularin group are compared with the control group;the above indicators of the Rivularin+oe-HOXA11-AS group are compared with the Rivularin group;Rivularin+oe-HOXA11-AS+XAV939 group compared with the Rivularin+oe-HOXA11-AS group,the differences were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion Rivularin regulates the occurrence and metastasis of lung squamous cell carcinoma by inhibiting the Wnt/β-catenin signaling pathway through HOXA11-AS.
8.Expert consensus on the clinical application of efficient intelligent chromosomal karyotyping precise auxiliary diagnosis system
Hao WANG ; Juan WEN ; Yi LAI ; Lingqian WU
Chinese Journal of Medical Genetics 2024;41(9):1025-1031
Chromosomal karyotyping analysis has been considered as the gold standard for cytogenetic diagnosis and an effective measure for preventing birth defects. However, conventional karyotyping analysis relies heavily on manual recognition, which is time-consuming and labor-intensive. The application of an efficient intelligent chromosomal karyotyping precise auxiliary diagnosis system in clinical practice can significantly reduce the analysis time and greatly improve the efficiency, increase the detection rate for low-percentage mosaicisms, and promote homogenization between laboratories. This can effectively enhance the capacity and level of cytogenetic diagnosis. With the continuous application of such system in the field of karyotyping analysis, a substantial amount of clinical application data and experience has been accumulated. This consensus has been formulated after multiple rounds of discussion by experts from the clinical application collaboration group of the efficient intelligent chromosomal karyotyping precise auxiliary diagnosis system. It aims to provide a reference for peers to better utilize intelligent auxiliary diagnosis systems during chromosomal karyotyping analysis and promote the standardized development of karyotyping analysis technology.
9.Effects of tumor location and mismatch repair on clinicopathological features and survival for non‐metastatic colon cancer: A retrospective, single center, cohort study
Zhen SUN ; Weixun ZHOU ; Kexuan LI ; Bin WU ; Guole LIN ; Huizhong QIU ; Beizhan NIU ; Xiyu SUN ; Junyang LU ; Lai XU ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2024;27(6):591-599
Objective:To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers.Methods:This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two‐thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left‐sided colon cancers (LCCs). Clinicopathological features were compared using the χ 2 test or Mann‐Whitney U test. Survival was estimated by Kaplan‐Meier curves and the log‐rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results:The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ 2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m 2 vs. 23.2 [21.3, 25.5] kg/m 2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ 2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ 2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ 2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow‐up time for all patients was 48 (range 33, 59) months. The log‐rank test revealed no significant differences in disease-free survival (DFS) ( P=0.668) or overall survival (OS) ( P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204?0.862, P=0.018), whereas a higher proportion of T3‐4 (HR=2.178, 95%CI: 1.089?4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443?3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115?3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146?0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103?1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log‐rank test revealed no significant differences in DFS ( P=0.343) or OS ( P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS ( P=0.047) and OS ( P=0.040) than did patients with pMMR. Conclusions:Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.
10.Impacts of participation in surgical clinical trial on safety and survival outcomes in patients with right-sided colon cancer
Huaqing ZHANG ; Guoqiang WANG ; Bin WU ; Guole LIN ; Huizhong QIU ; Beizhan NIU ; Junyang LU ; Lai XU ; Xiyu SUN ; Guannan ZHANG ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2024;27(9):928-937
Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.

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