Objective To explore the prognostic factors for patients with descending duodenum gastrointestinal stromal tumors (GIST), analyze the impact of different surgical approaches on prognosis, and develop a predictive model for surgical approach selection. Methods This single-center retrospective cohort study included patients with primary descending duodenum GIST treated in Zhongshan Hospital, Fudan University from January 2010 to January 2015, with follow-up until August 2025. The primary outcomes were incidence of postoperative complications, disease-free survival (DFS) rate, and overall survival (OS) rate. Cox regression and logistic regression were used to identify factors influencing prognosis and surgical approach selection, respectively. A nomogram model for selecting the surgical approach was constructed. Results A total of 78 patients with descending duodenum GIST were included, with age of (56.14±11.76) years. The 1-, 5-, and 10-year OS rates were 100%, 98.7%, and 85.7%, respectively, and the corresponding DFS rates were 100%, 90.9%, and 82.3%. Intraoperative blood loss, postoperative gastroparesis, mucosal ulceration, maximum tumor diameter, and Ki-67-positive cell ratio were independent risk factors for DFS, while maximum tumor diameter and mitotic figure were independent risk factors for OS (P＜0.05). The 10-year DFS rate was higher in the local resection group than in the pancreaticoduodenectomy group (89.45% vs 74.24%; HR＝0.300, P＝0.013), but there was no statistical difference in OS between the two groups. The incidence of postoperative complications in the pancreaticoduodenectomy group was higher than that in the local resection group (P＜0.001). Maximum tumor diameter and distance from tumor to the duodenal papilla were independent factors influencing surgical approach selection. The nomogram model based on these two indices demonstrated good discrimination and accuracy upon internal validation. Conclusions The long-term prognosis of patients with descending duodenal GIST is favorable, and surgical treatment achieves satisfactory outcomes. The nomogram model developed in this study can effectively guide individualized surgical approach selection and provide a reference for clinical decision-making.

Objective:To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification.Methods:A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically.Results:There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant ( P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference ( P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant ( P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant ( P<0.001). Conclusions:GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

As tumors originated from mesenchymal tissue, gastrointestinal stromal tumors (GIST) has its own typical history. For the idea of treatment for GIST at different historical periods, the role and value of surgery for the treatment of GIST keep changing. Laparoscopy and endoscopy will have the role they deserved. With the understanding of pathogenesis of GIST, targeted chemotherapy will be more and more accurate and individualized. How to improve the overall therapeutic effect of GIST, especially for the patients with the high risk and drug-resistance, is the dilemma and challenges for the surgeons.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Surgical resection is the only curative treatment, while imatinib is the first-line therapy for recurrent, metastatic, and unresectable GIST. However, more than half of GIST patients suffer from secondary resistance to imatinib within 2 years after treatment initiation. Therefore, early diagnosis, drug resistance and recurrence surveillance are critical for GIST patients. Liquid biopsy is a new method which utilizes the detection of tumor biomarkers in peripheral blood for early diagnosis and therapeutic efficacy assessment. In recent years, liquid biopsy has achieved significant research progress in several kinds of malignancy. This review aims at presenting an overview on research advance of liquid biopsy in GIST and may provide a new method for early diagnosis and therapeutic efficacy assessment of GIST.

Objective:Platelet-derived growth factor α (PDGFRA)-mutant gastrointestinal stromal tumor (GIST) is a relatively rare disease, whose clinicopathological characteristics and prognosis have been poorly studied. In this paper, the clinicopathological features and prognostic factors of PDGFRA-mutant GIST are investigated to provide more data for its understanding and treatment. Methods:A retrospective case-control study was used to collect the medical records of patients with GIST who underwent surgical resection in Zhongshan Hospital of Fudan University from January 2015 to August 2019. Patients with PDGFRA-mutant GIST were enrolled, and those with synonymous PDGFRA mutations, non-tumor-related deaths, and lack of clinicopathological data were excluded. The clinicopathological data were collected and the risk factors associated with prognosis were analyzed.Results:Among the enrolled 59 patients, there were 41 males (69.5%) and 18 females (30.5%) with the median age of 60 (25-79) years. All tumors originated from the stomach. The tumor size was 5 (3-7) cm, and the mitotic count was 2 (1-4)/50 high-power fields (HPF). According to the modified NIH risk stratification, 8 cases were classified as very low risk (13.6%), 25 cases as low risk (42.4%), 14 cases as moderate risk (23.7%), and 12 cases as high risk (20.3%). There were 7 cases of exon 12 mutation and 52 cases of exon 18 mutation (including 36 cases of D842V mutation). A comparison of clinicopathological features between the D842V mutation group and the non-D842V mutation group showed no statistically significant difference (all P>0.05). During a median follow-up of 21 (0-59) months, the 1- and 3-year relapse-free survival (RFS) rates of all the patients were 96.6% and 91.5%, respectively. There were 8 cases of recurrence and 3 cases of death. Six GIST patients with D842V mutation had tumor recurrence after operation, of whom 4 cases achieved varying degrees of tumor remission after being treated with dasatinib or avapritinib. Log-rank analysis showed that the overall survival (OS) of male was better than that of female (100% vs. 83.3%, P=0.046), but there was no significant difference in OS among patients with different risk grades ( P=0.057). The RFS and OS of patients with D842V mutation and non-D842V mutation, exon 12 and exon 18 mutation were similar (all P>0.05). Univariate Cox analysis showed that RFS was associated with gender ( P=0.010), tumor size ( P=0.042), mitotic count ( P=0.003), and the modified NIH risk stratification ( P=0.042), while multivariate analysis revealed that higher risk grade was an independent risk factor for recurrence of PDGFRA-mutant GIST (HR=12.796, 95%CI: 1.326-123.501, P=0.028). Gender was an independent factor for recurrence, and the risk of recurrence in males was lower than that in females (HR=0.154, 95%CI: 0.028-0.841, P=0.031). Conclusions:Gender and the modified NIH risk stratification are independent risk factors for recurrence of PDGFRA-mutant GIST, while patients with D842V and non-D842V mutation, and exon 12 and exon 18 mutation have a similar risk of recurrence and death.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Surgical resection is the only curative treatment, while imatinib is the first-line therapy for recurrent, metastatic, and unresectable GIST. However, more than half of GIST patients suffer from secondary resistance to imatinib within 2 years after treatment initiation. Therefore, early diagnosis, drug resistance and recurrence surveillance are critical for GIST patients. Liquid biopsy is a new method which utilizes the detection of tumor biomarkers in peripheral blood for early diagnosis and therapeutic efficacy assessment. In recent years, liquid biopsy has achieved significant research progress in several kinds of malignancy. This review aims at presenting an overview on research advance of liquid biopsy in GIST and may provide a new method for early diagnosis and therapeutic efficacy assessment of GIST.

Objective:Platelet-derived growth factor α (PDGFRA)-mutant gastrointestinal stromal tumor (GIST) is a relatively rare disease, whose clinicopathological characteristics and prognosis have been poorly studied. In this paper, the clinicopathological features and prognostic factors of PDGFRA-mutant GIST are investigated to provide more data for its understanding and treatment. Methods:A retrospective case-control study was used to collect the medical records of patients with GIST who underwent surgical resection in Zhongshan Hospital of Fudan University from January 2015 to August 2019. Patients with PDGFRA-mutant GIST were enrolled, and those with synonymous PDGFRA mutations, non-tumor-related deaths, and lack of clinicopathological data were excluded. The clinicopathological data were collected and the risk factors associated with prognosis were analyzed.Results:Among the enrolled 59 patients, there were 41 males (69.5%) and 18 females (30.5%) with the median age of 60 (25-79) years. All tumors originated from the stomach. The tumor size was 5 (3-7) cm, and the mitotic count was 2 (1-4)/50 high-power fields (HPF). According to the modified NIH risk stratification, 8 cases were classified as very low risk (13.6%), 25 cases as low risk (42.4%), 14 cases as moderate risk (23.7%), and 12 cases as high risk (20.3%). There were 7 cases of exon 12 mutation and 52 cases of exon 18 mutation (including 36 cases of D842V mutation). A comparison of clinicopathological features between the D842V mutation group and the non-D842V mutation group showed no statistically significant difference (all P>0.05). During a median follow-up of 21 (0-59) months, the 1- and 3-year relapse-free survival (RFS) rates of all the patients were 96.6% and 91.5%, respectively. There were 8 cases of recurrence and 3 cases of death. Six GIST patients with D842V mutation had tumor recurrence after operation, of whom 4 cases achieved varying degrees of tumor remission after being treated with dasatinib or avapritinib. Log-rank analysis showed that the overall survival (OS) of male was better than that of female (100% vs. 83.3%, P=0.046), but there was no significant difference in OS among patients with different risk grades ( P=0.057). The RFS and OS of patients with D842V mutation and non-D842V mutation, exon 12 and exon 18 mutation were similar (all P>0.05). Univariate Cox analysis showed that RFS was associated with gender ( P=0.010), tumor size ( P=0.042), mitotic count ( P=0.003), and the modified NIH risk stratification ( P=0.042), while multivariate analysis revealed that higher risk grade was an independent risk factor for recurrence of PDGFRA-mutant GIST (HR=12.796, 95%CI: 1.326-123.501, P=0.028). Gender was an independent factor for recurrence, and the risk of recurrence in males was lower than that in females (HR=0.154, 95%CI: 0.028-0.841, P=0.031). Conclusions:Gender and the modified NIH risk stratification are independent risk factors for recurrence of PDGFRA-mutant GIST, while patients with D842V and non-D842V mutation, and exon 12 and exon 18 mutation have a similar risk of recurrence and death.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Though surgical resection is the only radical treatment, postoperative recurrence and metastasis often occur. The first-line therapy for the treatment of recurrent, metastatic and unresectable GIST is imatinib. More than 80% of patients can benefit from imatinib treatment, but half of patients will still have recurrence or metastasis within 2 years after treatment initiation, and secondary drug resistance is a major cause of disease progression. Therefore, adeep understanding of the mechanisms of secondary drug resistance will guide us to develop personalized therapeutic schedule in the future. This article describes the mechanism of IM secondary resistance from the aspects of gene alteration, abnormal activation of signal transduction pathway, autophagy, apoptosis and drug concentration. It is found that single drug therapy has certain limitations in patients with secondary resistance to IM. Using IM combined with downstream signaling molecule inhibitors, autophagy inhibitors, insulin-like growth factor 1 receptor (IGF-1R) inhibitors, heat shock protein 90 (HSP90) inhibitors, cytotoxic T lymphocyte - associated antigen - 4 (CTLA - 4) antibodies and mitochondrial inhibitors provide us new therapeutic ideas. However, these combination treatments are still in the research phase, and further trials are needed to confirm the safety and efficacy. With the gradual deepening of research on drug resistance mechanisms, it will provide more solutions to the current serious drug resistance problem.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Though surgical resection is the only radical treatment, postoperative recurrence and metastasis often occur. The first?line therapy for the treatment of recurrent, metastatic and unresectable GIST is imatinib. More than 80% of patients can benefit from imatinib treatment, but half of patients will still have recurrence or metastasis within 2 years after treatment initiation, and secondary drug resistance is a major cause of disease progression. Therefore, adeep understanding of the mechanisms of secondary drug resistance will guide us to develop personalized therapeutic schedule in the future. This article describes the mechanism of IM secondary resistance from the aspects of gene alteration, abnormal activation of signal transduction pathway, autophagy, apoptosis and drug concentration. It is found that single drug therapy has certain limitations in patients with secondary resistance to IM. Using IM combined with downstream signaling molecule inhibitors, autophagy inhibitors, insulin?like growth factor 1 receptor (IGF?1R) inhibitors, heat shock protein 90 (HSP90) inhibitors, cytotoxic T lymphocyte ? associated antigen ? 4 (CTLA ? 4) antibodies and mitochondrial inhibitors provide us new therapeutic ideas. However, these combination treatments are still in the research phase, and further trials are needed to confirm the safety and efficacy. With the gradual deepening of research on drug resistance mechanisms, it will provide more solutions to the current serious drug resistance problem.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Though surgical resection is the only radical treatment, postoperative recurrence and metastasis often occur. The first?line therapy for the treatment of recurrent, metastatic and unresectable GIST is imatinib. More than 80% of patients can benefit from imatinib treatment, but half of patients will still have recurrence or metastasis within 2 years after treatment initiation, and secondary drug resistance is a major cause of disease progression. Therefore, adeep understanding of the mechanisms of secondary drug resistance will guide us to develop personalized therapeutic schedule in the future. This article describes the mechanism of IM secondary resistance from the aspects of gene alteration, abnormal activation of signal transduction pathway, autophagy, apoptosis and drug concentration. It is found that single drug therapy has certain limitations in patients with secondary resistance to IM. Using IM combined with downstream signaling molecule inhibitors, autophagy inhibitors, insulin?like growth factor 1 receptor (IGF?1R) inhibitors, heat shock protein 90 (HSP90) inhibitors, cytotoxic T lymphocyte ? associated antigen ? 4 (CTLA ? 4) antibodies and mitochondrial inhibitors provide us new therapeutic ideas. However, these combination treatments are still in the research phase, and further trials are needed to confirm the safety and efficacy. With the gradual deepening of research on drug resistance mechanisms, it will provide more solutions to the current serious drug resistance problem.