1.Diagnostic value of endoscopic ultrasound-guided tissue acquisition with rapid on-site evaluation performed by endoscopists in immunohistochemistry-required solid pancreatic lesions
Dingkun XIONG ; Yongru LIU ; Yunlu FENG ; Yu ZHAO ; Xi WU ; Tao GUO ; Qingwei JIANG ; Qiang WANG ; Dongsheng WU ; Shengyu ZHANG ; Yingyun YANG ; Aiming YANG
Chinese Journal of Pancreatology 2024;24(1):39-44
		                        		
		                        			
		                        			Objective:To evaluate the diagnostic value of rapid on-site evaluation (ROSE) performed by endoscopists for solid pancreatic lesions requiring tissue for immunohistochemistry (IHC) staining with different approach of endoscopic ultrasound-guided tissue acquisition (EUS-TA).Methods:After screening 1 573 cases who underwent EUS-TA operation at the Endoscopy Center of Peking Union Medical College Hospital between August 2018 and October 2022, a total of 65 cases of solid pancreatic lesions whose diagnosis rely on IHC staining was collected and summarized with clinical data of each case. Among 65 cases, there were 46 cases of pancreatic neuroendocrine tumors (PNETs), 13 cases of pancreatic solid pseudo-papillary tumors (SPTs), and 6 cases of lymphomas and mesenchymal. Patients were categorized into ROSE group (36 cases) and non-ROSE group (29 cases) according to the presence or absence of endoscopists performed ROSE during EUS-TA operation. They were further divided into subgroups of FNA-ROSE (26 cases), FNB-ROSE (10 cases), FNA-non-ROSE (24 cases) and FNB-non-ROSE (5 cases) according to the type of EUS-TA. Diagnostic accuracy and IHC success rate were compared between different groups and subgroups. Binomial logistic multifactorial regression analysis was used to evaluate the influence of ROSE and EUS-TA type on diagnostic accuracy and IHC success rate.Results:There were no statistically significant differences between ROSE group and non-ROSE group in terms of age, gender, bilirubin level, CA19-9 level, lesion site, lesion size, composition ratio of diagnosis, and surgical rate. The differences in mean size of lesions, needle gauge, location of puncturation, and number of needle pass between subgroups were not statistically significant. The diagnostic accuracy was 88.9% in ROSE group and 79.3% in non-ROSE group, and the difference between the two groups was statistically significant ( P=0.023). The diagnostic accuracy of FNA-ROSE group was higher than that of FNA-non-ROSE group (88.5% vs 75.0%), but the difference was not statistically significant ( P>0.100). The differences in diagnostic accuracy and success rate of IHC between FNB-ROSE group and FNB-non-ROSE group were not statistically significant. Binomial logistic multifactorial regression analysis did not reveal any independent influences on diagnostic accuracy. Conclusions:ROSE performed by endoscopists improved diagnostic accuracy of EUS-TA in solid pancreatic lesions requiring IHC staining, and therefore is potentially valuable for improving the diagnostic efficiency of EUS-TA for such diseases.
		                        		
		                        		
		                        		
		                        	
2.The Efficacy of Combined Endoscopic Ultrasound Fine-needle Aspiration and Endoscopic Retrograde Cholangiopancreatography in Same Session for the Diagnosis and Management of Pancreatic Carcinoma with Obstructive Jaundice
Yizhou ZHAO ; Jianing LI ; Qiang WANG ; Dongsheng WU ; Shengyu ZHANG ; Xi WU ; Tao GUO ; Qingwei JIANG ; Yingyun YANG ; Wen SHI ; Yunlu FENG ; Aiming YANG
Medical Journal of Peking Union Medical College Hospital 2024;15(4):819-824
		                        		
		                        			
		                        			 To explore the application value of endoscopic ultrasound fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment ofpatients with pancreatic cancer combined with obstructive jaundice. Clinical data of patients hospitalized in the Department of Gastroenterology of Peking Union Medical College Hospital who underwent ERCP biliary stent drainage for pancreatic cancer combined with obstructive jaundice from January 1, 2023 to February 26, 2024 were retrospectively collected. They were categorized into the fusion technology group and the simple ERCP group according to whether EUS-FNA was performed in the same endoscopic unit. The differences in pathologic diagnosis rate, ERCP drainage success rate, postoperative complication rate and patients' single hospitalization time were compared between the two groups. A total of 161 patients with pancreatic cancer combined with obstructive jaundice who underwent ERCP biliary stent drainage meeting the inclusion and exclusion criteria were enrolled, of which 80 were in the fusion technique group and 81 were in the simple ERCP group. The pathological diagnosis rate in the fusion technique group was higher than that in the simple ERCP group[92.50%(74/80)  The fusion of EUS-FNA and ERCP enhances the efficiency of diagnosis and treatment for pancreatic carcinoma, warranting widespread adoption and further research.
		                        		
		                        	
3.The role of endoscopic ultrasonogaphy in differentiating between autoimmune pancreatitis and pancreatic cancer
Tao GUO ; Tao XU ; Yamin LAI ; Shengyu ZHANG ; Xi WU ; Dongsheng WU ; Yunlu FENG ; Qingwei JIANG ; Qiang WANG ; Jiaming QIAN ; Aiming YANG
Chinese Journal of Digestive Endoscopy 2022;39(8):621-627
		                        		
		                        			
		                        			Objective:To investigate the role of endoscopic ultrasonography (EUS) in differentiating between autoimmune pancreatitis (AIP) and pancreatic cancer (PC).Methods:Data of 133 patients with AIP and 113 patients with PC who underwent EUS because of obstructive jaundice at Peking Union Medical College Hospital from January 2013 to December 2018 were retrospectively analyzed in the study, and were randomly divided into either a derivation sample or a validation sample using 1∶1 allocation according to the random number. In the derivation sample, 10 EUS characteristics were used to construct a prediction model to distinguish between AIP and PC, in which predictors were identified by multivariate stepwise logistic regression analysis and predictive efficacy was evaluated by receiver operating characteristics (ROC) curve analysis. The predictive efficacy was assessed in the validation sample. In view of the subjectivity in the judgment of diffuse/focal hypoechogenicity, 2 prediction models were designed in order to avoid bias.Results:By multivariate stepwise logistic regression analysis, diffuse hypoechogenicity ( OR=591.0, 95% CI: 98.8->999.9, P<0.001) and vessel involvement ( OR=11.9, 95% CI: 1.4-260.2, P=0.023) were identified as statistically significant predictors for distinguishing AIP from PC. EUS characteristics excluding diffuse/focal hypoechogenicity were stepped by logistic regression, which showed that hyperechoic foci/strands ( OR=177.3, 95% CI: 18.7->999.9, P<0.001), pancreatic duct dilation ( OR=60.5, 95% CI: 6.2->999.9, P=0.004), bile duct wall thickening ( OR=35.4, 95% CI: 3.7->999.9, P=0.009), lymphadenopathy ( OR=16.8, 95% CI: 1.7-475.2, P=0.038) and vessel involvement ( OR=22.7, 95% CI: 2.0-725.7, P=0.028) were statistically significant predictors to distinguish the two diseases. Both prediction models were built in the derivation sample, with area under the ROC curve of 0.995 and 0.979 respectively. In the validation sample, sensitivity, specificity, accuracy, positive predictive value and negative predictive value of both prediction models were all >90% by using the optimal cutoff value. Even for discrimination between focal AIP and PC, sensitivity and accuracy of both models were >90%, and specificity, positive predictive value and negative predictive value were all >85%. Conclusion:The 2 prediction models have good differential predictive value, and EUS is a useful tool to differentiate between AIP and PC.
		                        		
		                        		
		                        		
		                        	
4.Analysis of the endoscopic screening results of Beijing-Tianjin-Hebei Region Gastrointestinal Endoscopy Medical Association from 2016 to 2020
Meizi LI ; Shengyu ZHANG ; Ruoyu JI ; Dong WU ; Xi WU ; Tao GUO ; Qiang WANG ; Qingwei JIANG ; Yunlu FENG ; Dongsheng WU ; Yingyun YANG ; Aiming YANG ; Zhijie FENG ; Wen LI
Chinese Journal of Digestive Endoscopy 2022;39(11):889-894
		                        		
		                        			
		                        			Objective:To evaluate the development and application of gastrointestinal endoscopy technology in Beijing-Tianjin-Hebei (BTH) region from 2016 to 2020, and the impact of the corona virus disease 2019 (COVID-19) epidemic on gastrointestinal endoscopy screening and lesion detection rate of medical institutions.Methods:Data of gastroscopy and colonoscopy cases from 26 cooperative institutions in BTH Region Gastrointestinal Endoscopy Medical Association from January 2016 to December 2020 were collected by questionnaire. The number of gastrointestinal endoscopy, the detection of main lesions (including upper gastrointestinal malignant tumors, early gastric cancer and colon cancer), and the number of endoscopic treatment were retrospectively analyzed by year.Results:From 2016 to 2019, the number of gastroscopy and colonoscopy showed a yearly increasing trend with an annual growth rate of over 10%. Compared with 2019, the number of gastroscopy and colonoscopy decreased by 10.86% and 8.29%, respectively, in 2020 due to the impact of the epidemic. The annual detection rates of upper gastrointestinal malignant tumors, early gastric cancer and colon cancer were on a rise, from 7.22%, 1.49% and 8.98% in 2016 to 9.87%, 2.71% and 12.04% in 2020, respectively. The number of gastroscopic mucosal resection, submucosal dissection and colonoscopic endoscopic submucosal dissection increased yearly, from 2 132, 300 and 217 cases in 2016 to 5 466, 872 and 560 cases in 2020, respectively.Conclusion:The Medical Association has promoted the expansion of endoscopic screening and the application of endoscopic treatment techniques, resulting in a continuous increase in the endoscopy detection rate and early cancer diagnosis rate in the BTH region. The sharp decrease of gastrointestinal endoscopy procedures and the increase in the lesion detection rate in 2020 reflect the impact of epidemic COVID-19 on detection of gastrointestinal cancers.
		                        		
		                        		
		                        		
		                        	
5.Molecular pathology and clinical implications of diffuse glioma
Ruichao CHAI ; Shengyu FANG ; Bo PANG ; Yuqing LIU ; Yongzhi WANG ; Wei ZHANG ; Tao JIANG
Chinese Medical Journal 2022;135(24):2914-2925
		                        		
		                        			
		                        			The prognosis for diffusely infiltrating gliomas at World Health Organization (WHO) grade 2-4 remains dismal due to their heterogeneity. The rapid development of genome-wide molecular-profiling-associated studies has greatly promoted the accuracy of glioma classification. Thus, the latest version of the WHO classification of the central nervous system tumors published in 2021 has incorporated more molecular biomarkers together with histological features for the diagnosis of gliomas. Advanced usage of molecular pathology in clinical diagnostic practice provides also new opportunities for the therapy of patients with glioma, including surgery, radiotherapy and chemotherapy, targeted therapy, immunotherapy, and more precision clinical trials. Herein, we highlight the updates in the classification of gliomas according to the latest WHO guidelines and summarize the clinically relevant molecular markers by focusing on their applications in clinical practice. We also review the advances in molecular features of gliomas, which can facilitate the development of glioma therapies, thereby discussing the challenges and future directions of molecular pathology toward precision medicine for patients with glioma.
		                        		
		                        		
		                        		
		                        	
6.Endoscopic characteristics in predicting prognosis of biopsy-diagnosed gastric low-grade intraepithelial neoplasia.
Long ZOU ; Qingwei JIANG ; Tao GUO ; Xi WU ; Qiang WANG ; Yunlu FENG ; Shengyu ZHANG ; Weigang FANG ; Weixun ZHOU ; Aiming YANG
Chinese Medical Journal 2021;135(1):26-35
		                        		
		                        			BACKGROUND:
		                        			Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identify malignancies misdiagnosed as LGIN by biopsy and LGIN at high risk of progression.
		                        		
		                        			METHODS:
		                        			The clinical records of patients diagnosed with gastric LGIN by endoscopic biopsy who underwent at least two endoscopies during the first year of follow-up between 2007 and 2017 were retrospectively collected. Three endoscopists reviewed photographs of the initial endoscopy, described lesion characteristics, and made endoscopic diagnoses. Logistic regression was used to analyze predictors to identify malignancies underestimated as LGIN. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of these predictors. Patient clinical outcomes of follow-up >1 year were collected. Kaplan-Meier estimates with log-rank tests and Cox proportional hazards regression were used to analyze predictors of progression.
		                        		
		                        			RESULTS:
		                        			Overall, 48 of 182 (26.4%) patients were proven to have malignancies. A single lesion, a large lesion size, and marked intestinal metaplasia (IM) were independent predictors of initially misdiagnosed malignancies. The area under the curve of these predictors was 0.871, with a sensitivity of 68.7% and specificity of 92.5%. Twelve of 98 patients (12.2%) progressed during the 33-month median follow-up period. A whitish appearance, irregular margins, marked IM, and histological diagnosis of LGIN more than twice within the first year were predictors for progression.
		                        		
		                        			CONCLUSIONS
		                        			Lesions diagnosed as LGIN by biopsy with marked IM and other predictors above should be prudently treated for high potential to be malignancies or progress. Endoscopic follow-up with repeated biopsies within the first year is recommended.
		                        		
		                        		
		                        		
		                        			Biopsy
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		                        			Carcinoma in Situ
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		                        			Endoscopy
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		                        			Humans
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		                        			Prognosis
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		                        			Retrospective Studies
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		                        			Stomach Neoplasms/diagnosis*
		                        			
		                        		
		                        	
7.Risk factors for bleeding during gastric endoscopic submucosal dissection
Qiang WANG ; Xi WU ; Qingwei JIANG ; Tao GUO ; Yunlu FENG ; Dongsheng WU ; Shengyu ZHANG ; Aiming YANG
Chinese Journal of Digestive Endoscopy 2021;38(6):428-433
		                        		
		                        			
		                        			Objective:To summarize the clinical characteristics of bleeding during endoscopic submucosal dissection (ESD) and to analyze the risk factors for bleeding.Methods:Data of patients who received gastric ESD in endoscopy center of Peking Union Medical College Hospital from January 2015 to December 2019 were reviewed. The medical history, characteristics of gastric lesions, operation process and prognosis of the patients were analyzed.Results:A total of 437 gastric lesions of 422 patients were included in this study, and 406 lesions were gastric epithelial tumors. The bleeding rate during ESD was 32.3% (141/437), including 2 cases of acute massive hemorrhage. Intraoperative hemorrhage during ESD increased the incidence of myometrial injury and intraoperative perforation, and prolonged the operation time. Multivariate regression analysis showed that risk factors for bleeding during ESD were anatomical adhesion, the lesion location in the upper and middle 2/3 of the stomach, the lesion area ≥ 15 cm 2, male, and non-ESD absolute indications. Conclusion:Bleeding is the speed limiting factor for gastric ESD. For male patients, when the lesion is located in the upper and middle 2/3 of the stomach, large with anatomical adhesion during operation, precaution should be taken for intraoperative hemorrhage.
		                        		
		                        		
		                        		
		                        	
8.Evaluation of training mode and effect of diagnosis and treatment of early gastric cancer for digestive specialists
Qiang WANG ; Xi WU ; Aiming YANG ; Yingyun YANG ; Tao GUO ; Qingwei JIANG ; Shengyu ZHANG
Chinese Journal of Digestive Endoscopy 2021;38(9):733-736
		                        		
		                        			
		                        			Objective:To explore the approach of continuing education for digestive specialists through the establishment of training mode for diagnosis and treatment of early gastric cancer and the evaluation of training effect.Methods:A total of 48 participants of 3 sessions in the training course of early gastric cancer in Peking Union Medical College Hospital from September 2019 to January 2020 were enrolled in this study. Effects of six training methods were evaluated subjectively and objectively by a questionnaire survey and an on-site test.Results:After the training course of early gastric cancer, the diagnostic awareness (100.0%, 48/48), basic theoretical knowledge (97.9%, 47/48), endoscopic diagnosis ability (95.8%, 46/48) and endoscopic operation skills (87.5%, 42/48) of early gastric cancer of the trainees were significantly improved.The most effective training sessions were endoscopic images recognition, lectures of theoretical knowledge, case discussion and hands-on workshop. The results of theoretical knowledge test (79.38±8.10 VS 48.33±9.96, t=-21.176, P<0.001)and image diagnosis test (81.50±8.32 VS 49.58±13.48, t=-15.408, P<0.001) after training were significantly improved compared with those of before. Conclusion:The systematic training program of early gastric cancer that includes a variety of training methods is effective and should be widely promoted in the continuing education of digestive specialists.
		                        		
		                        		
		                        		
		                        	
9.Effects of histone acetyltransferase MYST2 on pancreatic cancer
Wenzhen HAO ; Yunlu FENG ; Xi WU ; Shengyu ZHANG ; Qingwei JIANG ; Qiang WANG ; Tao GUO ; Dongsheng WU ; Dong WU ; Aiming YANG
Chinese Journal of Digestion 2021;41(8):561-567
		                        		
		                        			
		                        			Objective:To investigate the expression at protein level and diagnostic value of histone acetyltransferase MYST2 in pancreatic cancer.Methods:From December 1st, 2017 to June 30th, 2020, at Peking Union Medical College Hospital, a total of 54 cases of pancreatic cancer tissues and corresponding paracancerous pancreatic tissues (>5 cm from the surgical margin) resected and confirmed by pathology were collected. ASPC1 and BXPC3 pancreatic cancer cell lines were knocked down (ASPC1 and BXPC3 knockdown group), CFPAC1 and SW1990 pancreatic cancer cell lines were overexpressed (CFPAC1 and SW1990 overexpression group), the untreated ASPC1, BXPC3, CFPAC1 and SW1990 were set as blank vector control group. The expression at protein level of MYST2 was detected by Western blotting in patients with different degrees of pathological differentiation, human normal pancreatic duct epithelial cell line HPDE, human pancreatic cancer cell lines ASPC1, BXPC3, CFPAC1 and SW1990, knockdown group, overexpression group and blank vector control group. The cell proliferation, migration, invasion and colony formation ability of the knockdown group, overexpression group and blank vector control group were determined by real-time cellular analysis, Transwell migration and invasion test, and plate colony formation assay. MYST2 immunohistochemical scoring was performed on pancreatic cancer tissues and para cancer tissues. Receiver operating characteristic curve was drawn to analyze the value of different MYST2 protein expression levels in the diagnosis of pancreatic cancer. Independent sample t test and variance analysis were used for statistical analysis. Results:Among the pathological slides of 54 cases of pancreatic cancer, 13 cases were highly differentiated, 24 cases were moderately differentiated, 15 cases were poorly differentiated and 2 cases were undifferentiated, the MYST2 expression at protein level in pancreatic cancer cells was 3.12±1.67, 2.87±1.59, 2.12±1.03 and 1.08±0.34, respectively, and the difference was statistically significant ( F=1.241, P<0.05). The MYST2 expression levels of ASPC1, BXPC3, CFPAC1 and SW1990 were all higher than that of normal pancreatic ductal epithelial cell lines HPDE (1.41±0.47, 1.40±0.93, 1.13±0.62 and 1.71±0.46 vs. 0.82±0.25), and the differences were statistically significant( t=1.625, 1.577, 1.319 and 1.832, all P<0.05). The MYST2 expression level of BXPC3 knockdown group was lower than that of BXPC3 blank vector control group (0.39±0.12 vs. 0.75±0.34); that of ASPC1 knockdown group was lower than that of ASPC1 blank vector control group (0.43±0.22 vs. 0.82±0.48); that of CFPAC1 overexpression group was higher than that of CFPAC1 blank vector control group (1.38±0.45 vs. 0.82±0.37); that of SW1990 overexpression group was higher than that of SW1990 blank vector control group (1.34±0.65 vs. 0.51±0.22), and the differences were statistically significant ( t=1.414, 1.378, 1.319 and 1.934, all P<0.05). The cell proliferation of ASPC1 knockdown group was slower than that of ASPC1 blank vector control group, and the proliferation peak at 80 h was lower than that of blank vector control group (1.02±0.77 vs. 4.31±2.45); the cell proliferation of BXPC3 knockdown group was slower than that of BXPC3 blank vector control group, and the proliferation peak at 80 h was lower than that of blank vector control group (0.91±0.24 vs. 2.84±0.53); the proliferation of pancreatic cancer cells in SW1990 overexpression group was faster than that of SW1990 blank vector control group, and the proliferation peak at 80 h was higher than that of blank vector control group (3.10±0.67 vs. 1.04±0.17); the proliferation of pancreatic cancer cells in CFPAC1 overexpression group was faster than that that of CFPAC1 blank vector control group, and the proliferation peak at 80 h was higher than that of blank vector control group (5.45±1.13 vs. 1.01±0.29), and the differences were statistically significant ( t=1.427, 1.316, 1.292 and 1.501, all P<0.05). In the test of migration ability, the number of cells passed through the Transwell chamber of ASPC1 knockdown group was less than that of ASPC1 blank vector control group (34.08±17.62 vs. 118.76±5.31); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (18.62±9.64 vs. 57.90±12.67); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (134.84±24.65 vs. 37.82±6.73); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (65.79±27.46 vs. 11.68±5.13), and the differences were statistically significant ( t=1.475, 1.322, 1.437 and 1.219, all P<0.05). In the test of invasion ability, the number of cells passed through the Transwell chamber of ASPC1 knockdown group was less than that of ASPC1 blank vector control group (9.79±5.75 vs. 45.76±12.71); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (23.46±11.13 vs. 84.92±17.65); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (156.42±34.50 vs. 42.13±22.17); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (112.64±47.82 vs. 39.09±17.23), and the differences were statistically significant ( t=1.324, 1.635, 1.423 and 1.119, all P<0.05). The number of colony formation of the ASPC1 knockdown group was less than that of ASPC1 blank vector control group (13.15±6.42 vs. 86.79±35.17); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (14.93±9.30 vs. 52.93±15.76); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (129.10±57.31 vs. 62.42±37.43); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (157.98±66.45 vs. 74.35±34.69), and the differences were statistically significant ( t=1.148, 1.290, 1.274 and 1.462, all P<0.05). The MYST2 score of pancreatic cancer tissues was higher than that of adjacent paracancerous pancreatic tissues (3.04±2.23 vs. 1.32 ± 0.70), and the difference was statistically significant ( t=3.479, P<0.05). When the total immunohistochemistry score of MYST2 was 3 point, the area under the curve was the largest (0.888, 95% confidence interval 0.827 to 0.948), and the Youden index was 0.56. Conclusion:MYST2 is associated with the proliferation, invasion and migration of pancreatic cancer cells, and promotes the development of pancreatic cancer.
		                        		
		                        		
		                        		
		                        	
10.Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and evolution.
Zhaoshi BAO ; Yongzhi WANG ; Qiangwei WANG ; Shengyu FANG ; Xia SHAN ; Jiguang WANG ; Tao JIANG
Frontiers of Medicine 2021;15(4):551-561
		                        		
		                        			
		                        			Glioma is the most common lethal tumor of the human brain. The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months. The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas. Unlike primary glioblastoma that usually develop de novo in the elderly, secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis. Based on various evolutional trajectories brought on by clonal and subclonal alterations, the evolution patterns of glioma vary according to different theories. Some important features distinguish the normal brain from other tissues, e.g., the composition of the microenvironment around the tumor cells, the presence of the blood-brain barrier, and others. The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer. Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment. However, the detailed reasons for the progression and recurrence of glioma remain controversial. In this review, we introduce the different mechanisms involved in glioma progression, including tumor heterogeneity, the tumor microenvironment and drug resistance, and their pre-clinical implements in clinical trials. This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.
		                        		
		                        		
		                        		
		                        			Aged
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		                        			Brain Neoplasms/genetics*
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		                        			Drug Resistance
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		                        			Glioblastoma
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		                        			Glioma/genetics*
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		                        			Humans
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		                        			Mutation
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		                        			Neoplasm Recurrence, Local/drug therapy*
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		                        			Tumor Microenvironment
		                        			
		                        		
		                        	
            
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