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Objective:To investigate the clinicopathological characteristics of primary gastrointestinal stromal tumors (GIST) with PDGFRα mutation and analyze the prognosis of different subtypes.Methods:From Jun 2010 to Jun 2019, the clinicopathological data of 35 patients with primary PDGFRα mutation GIST, who underwent surgical therapy in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were analyzed retrospectively.Results:The main symptoms was abdominal pain (28 cases, 80%), followed by abdominal mass (6 cases, 17%), and hemafecia (1 case, 3%). 31 primary lesions (89%) were located in the stomach and 4 (11%) in other than stomach. 13 cases (37%) were of epithelioid cells, 14 cases (40%) were of spindle cells and 8 cases (23%) were of mixed cells. 27 cases (77%) were CD117 positive , 28 cases (80%) CD34 positive , and 30 cases (86%) were DOG-1 positive. 19 cases (54%) had D842V mutation and 16 cases (46%) had non-D842V mutation. Complete surgical resection was performed in all patients, with no perioperative death. The 3-year recurrence-free survival rate of the D842V mutation group was lower than that of the non-D842V mutation group (84% vs. 100%, P=0.045). Conclusions:The mutation rate of PDGFRα gene was low, mostly derived from the stomach. PDGFRα mutation GIST presents inert biological behavior and the overall prognosis was good.
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Objective@#To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration <1100 μg/L influences the efficacy of adjuvant therapy.@*Methods@#A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease - Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22-26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Patients were divided into <1100 μg/L group and ≥1100 μg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non-normal distribution were analyzed by Spearman correlation. Kaplan-Meier survival curves and COX regression model were used for survival analysis.@*Results@#Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m2 and body surface area was (1.6±0.2) m2. Thirty patients received gene test, including 23 patients with c-Kit exon 11 mutation, 4 with c-Kit exon 9 mutation, 1 with c-Kit exon 11 and 17 mutation and 2 without c-Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) μg/L, and there were 32 patients with plasma concentration <1100 μg/L and 53 patients with plasma concentration ≥1100 μg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow-up time was 30 (range 4-49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 μg/L and two with plasma concentration ≥1100 μg/L. One recurrent patient with plasma concentration <1100 μg/L was detected to harbor c-Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 μg/L were both detected to harbor c-Kit exon 9 mutation. The 3-year relapse-free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 μg/L, and 96.6% in patients with plasma concentration ≥1100 μg/L. No significant difference in relapse-free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration <1100 μg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022-2.637, P=0.242).@*Conclusions@#IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 μg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.
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Objective@#To investigate the efficacy and feasibility of laparoscopic resection for gastric gastrointestinal stromal tumor (GIST) in unfavorable location by comparing with open surgery.@*Methods@#Clinicopathological and follow-up data of 176 patients with gastric GIST in unfavorable location admitted at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2005 to December 2017 were analyzed retrospectively. There were 94 males and 82 females, aging of (57.4±12.7) years (range: 20-90 years). Of the 176 patients, 64 underwent laparoscopic surgery (laparoscopic group) and 112 underwent open surgery (open group). One-to-one propensity score matching (PSM) was performed to balance the covariance between laparoscopic group and open surgery group. Before PSM, the differences between the two group in tumor size and modified National Institutes of Health risk classification were significant. After PSM, there were 63 pairs (63 cases in laparoscopic group and 63 cases in open group) and the baseline characteristics were comparable between the two groups(P>0.05). The difference of short-term outcome between the two groups were compared using t test, χ2 test or Wilcoxon rank-sum test. The survival curve was established by Kaplan-Meier method and the Log-rank test was used to compare the survival of the two groups.@*Results@#The operation time of laparoscopic group was shorter ((141.6±100.6) minutes vs. (100.4±67.7) minutes, t=2.681, P=0.008), the hospitalization cost was higher ((5.2±0.7) ten thousand yuan vs. (4.2±0.8) ten thousand yuan, t=7.357, P=0.000) than open group. The time to first flatus ((49.1±8.2) hours vs. (71.0±4.6) hours, t=-18.482, P=0.000) and preoperative hospital stay ((10.3±6.0) days vs. (14.8±7.6) days, t=-3.717, P=0.000) was shorter in laparoscopic group. With a median follow-up time of 44 months (range: 10 to 154 months), the 1-, 3-, 5-year relapse-free survival rates in the laparoscopic group and open group were 98.3%, 92.1%, 92.1% and 100%, 86.3%, 83.2%, respectively (χ2=0.696, P=0.404). The 1-, 3-, 5-year overall survival rates in the laparoscopic group and open group were 96.6%, 94.7%, 94.7% and 100%, 91.1%, 81.4%, respectively (χ2=0.366, P=0.545).@*Conclusions@#In experienced medical centers, laparoscopic resection is safe and feasible for GIST in unfavorable location. Compared to open surgery, laparoscopic resection achieves a faster postoperative recovery and a similar long-term prognosis.
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Objective To explore the clinical prognosis and efficacy of adjuvant therapy with imatinib of postoperative patients with gastric intermediate-risk gastrointestinal stromal tumor (GIST).Methods The clinicopathological data and follow-up data of 93 gastric intermediate-risk GIST cases from Jan 2005 to Dec 2016 at Union Hospital were analyzed retrospectively.Univariate and multivariate analysis were performed to assess the prognostic factors.Results There were 93 patients undergoing complete GIST resection with 42(45％) cases receiving post-op imatinib 400 mg/d for targeted therapy.The median target therapy period was 12 (6-72) months.86％ (80 cases) patients were followed up for 46 (6-120) months.The 1-,3-,5-year recurrence-free survival rate (RFS) of the whole group were 100％,91.5％,88.5％ respectively.Multivariate analysis revealed that mitotic count (P =0.040,RR =6.078,95％ CI:0.541-68.274) and neutrophil-lymphocyte ratio (NLR) (P =0.036,RR =6.102,95％ CI:0.782-47.632) were prognostic risk factors of RFS.For those mitotic count ＞ 2/50 HPF and NLR ＞ 2.3,adjuvant therapy with imatinib significantly increases RFS.Conclusion Mitotic count and NLR were independent risk factors of RFS in gastric intermediate-risk GIST.For those with mitotic count ＞ 2/50 HPF and NLR ＞ 2.3,postoperative adjuvant therapy with imatinib helps improve the prognosis.
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Objective To investigate the clinical characteristics,treatment strategies and curative effect of recurrence and metastasis of primary gastrointestinal stromal tumor (GIST) after complete resection along with adjuvant therapy with imatinib,and to analyze the risk factors of recurrence and metastasis after adjuvant therapy.Methods The demographic data,clinicopathological characteristics and follow-up data of 80 primary GIST patients who received adjuvant therapy with imatinib for at least 1-year duration and had already stopped taking imatinib from January 2005 to December 2017 in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology were analyzed retrospectively.The survival analysis was performed using Kaplan-Meier approach.Univariate analysis was conducted using log-rank test.Multivariate analysis was produced by Cox regression model.Results Of the enrolled 80 patients,recurrence and metastasis were detected in 17 cases after completion of postoperative adjuvant therapy with imatinib,with a median recurrence time of 12 months.All the 17 patients showed no specific clinical manifestations.Liver metastasis,peritoneum metastasis and local recurrence were found in 9,5 and 3 cases,respectively.In the 17 patients with recurrence and metastasis,9 patients received imatinib monotherapy.Among the 9 patients,6 achieved partial responses,while 3 demonstrated stable disease,and secondary drug resistance was found in 7 patients during the follow-up period,with a median progression-free survival of 35 months (95％ CI:15-55 months) and median overall survival of 49 months (95％ CI:30-68 months).A total of 7 patients with recurrence and metastasis were treated with imatinib after operation and achieved satisfying tumor control,and secondary drug resistance was found in 4 patients during the follow-up period,with a median progression-free survival of 31 months (95％ CI:6-56 months) and fell short of median overall survival.The remaining 1 patient gave up treatment.Univariate analysis showed that tumor location (x2 =4.120,P =0.042),preoperative neutrophil-to-lymphocyte ratio (NLR) (x2 =7.513,P =0.006) and preoperative platelet-to-lymphocyte ratio (PLR) (x2 =6.575,P =0.010) were associated with recurrence and metastasis of GIST patients after completion of adjuvant therapy.Multivariate analysis revealed that tumor location (HR =3.787,95％ CI:1.126-12.732,x2 =4.631,P =0.031) was an independent prognostic factor for those patients.Conclusion GIST patients who are identified recurrence and metastasis after completion of adjuvant imatinib treatment show no specific clinical manifestations after stopping andjuvant therapy with imatinib.Compared with gastric GIST,non-gastric origin GIST has a higher risk of recurrence.Imatinib monotherapy and surgery combined with imatinib therapy are both effective in treating this subgroup of patients.
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Objective To investigate the clinical efficacy and safety of domestic imatinib in the treatment of gastrointestinal stromal tumor (GIST). Methods Clinicopathological and follow-up data of GIST patients who received domestic imatinib treatment from January 2014 to December 2017 in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were analyzed retrospectively. The treatment efficacy and adverse reactions were analyzed. Results A total of 35 patients included 20 males and 15 females with a median age of 53 years old (28-79 years old). Among all the patients, 25 with primary GIST underwent complete resection, in which 20 cases were classified as high risk and 5 as moderate risk according to the risk stratification. Of the remaining 10 recurrent/metastatic or unresectable GIST patients, 6 cases had metastasis in liver, 2 cases had metastasis in peritoneum, 1 case had extensive abdominal and pelvic metastasis, and the other 1 case was initially unresectable. The follow-up data of all the 35 patients were available, with a median follow-up time of 25 months (4-49 months). Twenty-five primary patients with complete resection received adjuvant therapy with a median time of 14 months (4-44 months). The median time of follow-up was 25 months (4-49 months), and none of the primary patients was detected with recurrence or metastasis of GIST. Meanwhile, of the 10 patients with recurrent/metastatic or unresectableGIST, the median time of medicine-taking was 24 months (3-49 months). Seven of 10 patients received imatinib monotherapy, including 5 cases of partial remission and 2 cases of stable disease. The other 3 patients with localized progression received complete resection along with imatinib therapy. All the 10 patients achieved durable clinical benefit. Twenty-seven patients (77.1％) experienced adverse events, and only 1 case (2.9 ％) had grade 3 adverse events. Conclusion Domestic imatinib is effective and safe for patients who received adjuvant therapy after complete resection of primary GIST as well as those with recurrent/metastatic or unresectable GIST, but it remains to be further confirmed by large samples of prospective studies.