Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm²), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.
Male ; Humans ; Gastrointestinal Stromal Tumors/surgery* ; Retrospective Studies ; Ki-67 Antigen ; Stomach Neoplasms/pathology* ; Prognosis ; Mutation ; Intestines/pathology* ; Proto-Oncogene Proteins c-kit/genetics* ; Receptor, Platelet-Derived Growth Factor alpha/genetics*

To explore the differences in biological characteristics for the small gastrointestinal stromal tumors and the incidence of complications and recurrence between the traditional surgical treatment and endoscopic treatment.
 Methods: We collected the relevant clinical and pathological data from patients who were diagnosed as gastrointestinal stromal tumors with the diameter less than 2 cm by the Department of Pathology of Xiangya Hospital from January 2009 to December 2015. The complications and recurrence after the surgical treatment were analyzed.
 Results: In patients with small gastrointestinal stromal tumors, the proportion of female was higher than that of male (male:female=1:1.69). The median age for patient with this disease was 49 years old and it was more common in middle-aged and elderly. Most lesions were found in the stomach, followed by the esophagus and the small intestine. The small gastrointestinal stromal tumors occurred in the colon and rectum were rare. There was 60.3% (47/78) patients with abdominal pain, 7.7% (6/78) patients with hematochezia or melena, and 98.7% (78/79) with small gastrointestinal stromal tumors' mitotic count ≤5/50 HPF. The positive rates for CD, CD34, DOG-1, actin-smooth, and S-100 were 98.7%, 86.1%, 82.3%, 31.6%, and 24.1%, respectively. Three patients occurred surgical complications, 2 suffered recurrence during the follow-up. There was no significant difference in the incidence of complications and recurrence between the traditional surgical treatment and endoscopic treatment (P>0.05).
 Conclusion: Small gastrointestinal stromal tumors' malignant potential is low, and the recurrence and metastasis rate is low. Its biological behavior tends to be benign. The traditional surgical treatment and endoscopic treatment are both safe and effective for small gastrointestinal stromal tumor. Endoscopic treatment has the advantages in lower cost, shorter hospitalization time, and small trauma. Therefore, endoscopic treatment could be the first choice for small GIST resection under the condition of mature endoscopic technology.
Aged ; Endoscopy, Gastrointestinal ; Female ; Gastrointestinal Hemorrhage ; etiology ; Gastrointestinal Neoplasms ; complications ; pathology ; surgery ; Gastrointestinal Stromal Tumors ; complications ; pathology ; surgery ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Postoperative Complications ; epidemiology ; Retrospective Studies ; Tumor Burden

OBJECTIVETo investigate the treatment methods and prognostic factors of high-risk gastrointestinal stromal tumor (GIST).

METHODSClinicopathological date and follow-up data of 108 patients with high-risk GIST from January 2002 to February 2016 treated at our department were retrospectively reviewed. The patients were divided into two groups according to whether they received adjuvant therapy after surgery. A group of patients received imatinib adjuvant therapy(adjuvant therapy group, 69 cases). Another group of patients were not treated with imatinib until they were found to have disease progression(follow-up observation group, 39 cases). The survival rate and recurrence rate were compared between two groups, and the risk factors of prognosis were analyzed by Cox regression model.

RESULTSAll the cases were followed up with a median time of 48 months(1 to 161 months). Recurrence and / or metastasis occurred in 57(52.8%) patients during follow-up. The postoperative recurrence and / or metastasis rate was 34.8%(24/69) and 84.6%(33/39) respectively in the adjuvant therapy group and the follow-up observation group, the difference was statistically significant(P=0.000). Twenty-eight(25.9%) patients died. The 1-, 3-, 5-, 10-year survival rates of the 108 patients undergoing follow-up were estimated to be 99.8%, 87.7%, 76.0% and 42.7% respectively. The 5-year survival rates were 79.3% and 72.3% in the adjuvant therapy group and the follow-up observation group, the difference was not statistically significant (P=0.648). Univariate analysis showed that mitotic count, radical degree and tumor rupture were predictive factors of survival after resection of primary high-risk GIST (all P<0.05). Multivariate analysis using Cox regression model revealed that the mitotic count (P=0.013, RR=2.400, 95%CI:1.206 to 4.779) and radical degree(P=0.003, RR=3.968, 95%CI:1.609 to 9.784) were independent prognostic factors.

CONCLUSIONComprehensive treatment of radical surgery combined with targeted therapy and close followed up can lead to better long-term survival of high-risk patients with GIST.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Combined Modality Therapy ; Disease Progression ; Female ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; drug therapy ; pathology ; surgery ; Humans ; Imatinib Mesylate ; therapeutic use ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Postoperative Period ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate

OBJECTIVETo investigate the efficacy of targeted therapy combined with surgery in the treatment of recurrent and metastatic gastrointestinal stromal tumor(GIST).

METHODSClinicopathological and followed-up data of 318 patients with recurrent and metastatic GIST admitted in Zhongshan Hospital between January 2000 and December 2015 were analyzed retrospectively. According to different treatment methods, the patients were divided into four groups: surgery group (operation alone, 44 cases), target therapy group (imatinib alone, 108 cases), target therapy combined with surgery group (imatinib plus operation, 139 cases), other therapy group (chemotherapy, Chinese medicine and others, 27 cases). The progression-free survival (PFS) and overall survival (OS) of four groups were compared.

RESULTSThe baseline informations, such as age, gender, primary site, et al, were not significantly different (all P>0.05), but the recurrent and metastatic site was significantly different among 4 groups (P=0.000). The medial PFS of surgery group, target therapy group, target therapy combined with surgery was 16(95%CI: 4.9 to 27.0) months, 44 (95%CI: 30.9 to 57.1) months, 35 (95%CI: 26.5 to 43.5) months, respectively, and the latter 2 groups had significantly longer PFS than surgery group(P=0.000), while no significant difference was found between target therapy group and target combined with surgery group (P=0.251). The median OS of surgery group, target therapy group, target therapy combined with surgery, and other therapy group was 24 (95%CI: 9.0 to 39.0) months, 69(95%CI: 40.8 to 97.2) months, 92(95%CI: 78.0 to 106.0) months, 12(95%CI: 9.5 to 14.5) months. Target therapy group and target therapy combined with surgery group had significantly longer OS than surgery and other therapy groups (P=0.000), while the target therapy combined with surgery group had significantly longer OS than target therapy group(P=0.028).

CONCLUSIONTarget therapy combined with surgery can prolong the survival of recurrent and metastatic GIST patients.

Antineoplastic Agents ; therapeutic use ; Benzamides ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Gastrointestinal Stromal Tumors ; drug therapy ; pathology ; surgery ; Humans ; Imatinib Mesylate ; therapeutic use ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Retrospective Studies

OBJECTIVETo retrospectively analyze the clinicopathology of patients with gastric gastrointestinal stromal tumor(gGIST) who underwent radical excision within 18 years in 10 domestic medical centers in order to understand the status of domestic surgical treatment of gGIST.

METHODSClinicopathological data of gGIST patients undergoing radical excision in 10 medical centers from January 1998 to January 2016 were collected, and their operational conditions, postoperative adjuvant therapy, gene detection and survival were analyzed retrospectively.

RESULTSA total of 1 846 cases were recruited in this study, including 246 cases from Guangdong General Hospital, 331 cases from Sun Yat-sen University Cancer Center, 374 cases from Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 342 cases from Nanfang Hospital of Southern Medical University, 265 cases from Fujian Medical University Union Hospital, 148 cases from Fudan University Shanghai Cancer Center, 49 cases from West China Hospital of Sichuan University, 43 cases from Peking University Cancer Hospital and Institute, 28 cases from the 81st Hospital of Pepole's Liberation Army(PLA), 20 cases from Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute. There were 918 male (49.7%) and 928 female patients (50.3%) with median onset age of 59(18 to 95) years old. Fundus(735 cases, 39.8%) and body (781 cases, 42.3%) of stomach were the common sites of lesions. The average size of tumor was (5.3±4.6) cm. There were 1 421 cases with mitotic count ≤5(77.0%). According to the operation procedure, 924 cases (50.1%) underwent laparoscopic surgery, 759 cases (41.1%) laparotomy, 120 cases (6.5%) endoscopic surgery, and 20 cases (1.1%) laparoscopic combined with endoscopic surgery, 6 cases (0.3%) laparoscopic excision surgery through gastric wall and cavity, and 17 cases (0.9%) laparoscopy and then were transferred to laparotomy. Wedge excision were performed in 1 308 cases (70.9%), proximal gastric excision in 226 cases(12.2%), distal gastric excision in 92 cases (5.0%), total gastrectomy in 94 cases (5.1%), and local gastrectomy in 126 cases(6.8%). Multi-visceral excision was performed in 138 cases, and the splenectomy was performed in 83 cases(60.1%)with the highest ratio. According to modified NIH classification, 399 cases(21.6%) were extreme low risk, 580 cases(31.4%) were low risk, 424 cases(23.0%) were moderate risk, 443 cases (24.0%) were high risk. A total of 461 cases received postoperative imatinib adjuvant therapy, accounting for 53.2%(461/867) of patients with moderate and high risk. Among 1 846 cases, 1 402 cases (75.9%) had complete follow-up data and the median follow-up time was 33.6 (0.1 to 158) months. The 5-year survival rates of extreme low risk, low risk, moderate risk and high risk were 100%, 98.5%, 92.5%, and 79.2% with significant difference(P=0.000).

CONCLUSIONSGastric GIST occurs mostly in fundus and body of stomach in China. Wedge excision is the main operational procedure and laparoscopic operation is over 50%. General prognosis of gastric GIST is quite good.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; China ; Combined Modality Therapy ; Female ; Gastrectomy ; Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; pathology ; surgery ; Humans ; Imatinib Mesylate ; therapeutic use ; Laparoscopy ; Laparotomy ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; Retrospective Studies ; Splenectomy ; Stomach Neoplasms ; pathology ; surgery ; Survival Rate ; Young Adult

No abstract available.
Adult ; Antineoplastic Agents/*adverse effects ; Antitubercular Agents/therapeutic use ; Biopsy ; Female ; Gastrointestinal Stromal Tumors/*drug therapy/pathology/surgery ; Humans ; Imatinib Mesylate/*adverse effects ; Lung Diseases, Interstitial/*chemically induced/diagnosis ; Mycobacterium tuberculosis/*isolation & purification ; Protein Kinase Inhibitors/*adverse effects ; Rectal Neoplasms/*drug therapy/pathology/surgery ; Tomography, X-Ray Computed ; Tuberculosis, Pulmonary/diagnosis/drug therapy/*microbiology

OBJECTIVETo analyze the efficacy and prognosis of different treatments on small intestinal gastrointestinal stromal tumors(SIGIST).

METHODSClinical data of 63 patients with SIGIST who were admitted to the Chinese PLA General Hospital from January 2004 to December 2013 were analyzed retrospectively. According to resection procedure and postoperative use of imatinib, patients were divided into R0 resection plus imatinib group (13 cases), R0 resection without imatinib group (42 cases), non-R0 resection plus imatinib group (7 cases), non-R0 resection without imatinib group (1 case). Survival was compared among groups. Result All the patients were followed up with a median length of 24 months(3 to 120 months), and the over survival (OS) rates at 1-year, 3-year, 5-year were 97%, 94% and 80%. In R0 resection plus imatinib group, R0 resection without imatinib group, and non-R0 resection plus imatinib group, the progression free survival(PFS) time was 24, 24 and 23 months; the 1-year PFS were 100%, 97% and 83%; the 3-year PFS were 100%, 45% and 83%; the 5-year PFS were 100%, 28% and 42%. R0 resection plus imatinib group had significantly higher PFS(all P<0.05). The case of non-R0 resection without imatinib died 6 months after operation. Among 55 patients undergoing R0 resection, recurrence was found in 16 patients, whose recurrence rates of 1-year, 3-yeart and 5-year were 2%,43% and 58%. Local recurrence was found in 8 cases, hepatic recurrence in 3 cases and widespread recurrence in 5 cases, who received simple imatinib, operation plus imatinib and imatinib intervention, with median survival time of 66.5 months, 92.5 months and 48 months respectively. One patient initiatively abandoned treatment and died 17 months later.

CONCLUSIONThe total resection and postoperative imatinib administration can improve the prognosis and raise the progression free survival of patients with small intestinal stromal tumors.

Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Disease-Free Survival ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; Intestinal Neoplasms ; drug therapy ; pathology ; surgery ; Intestine, Small ; pathology ; Neoplasm Recurrence, Local ; Piperazines ; therapeutic use ; Prognosis ; Pyrimidines ; therapeutic use ; Retrospective Studies

BACKGROUND/AIMS: Submucosal tumors of the esophagus are rare lesions among all esophageal neoplasms. The purpose of this study was to evaluate the clinicopathologic features of esophageal submucosal tumors treated by surgical approach. METHODS: We analyzed the clinicopathologic and endoscopic ultrasonographic features of 18 esophageal submucosal tumors which were treated by surgical approach at Boramae Medical Center and Seoul National University Bundang Hospital from January 2005 to June 2012. RESULTS: The mean age was 48.9 years old and male to female ratio was 2.6:1. Asymptomatic patients were most common (77.8%). In endoscopic ultrasonographic finding, the majority tumor arouse in the middle (55.6%) and lower (44.4%) esophagus, and appeared as hypoechoic lesion (72.2%) in the 4th layer (83.3%). The most common indication for surgical approach was unclear biological behavior of the tumor. Minimally-invasive technique using thoracoscopy was applied for the enucleation (83.3%). The mean diameter of the tumor was 5.4 cm, and the final diagnosis was leiomyoma (89.9%) and gastrointestinal stromal tumor (11.1%). CONCLUSIONS: Leiomyoma was the most common submucosal tumor in esophagus. However, endoscopic ultrasonography was not able to differentiate between leiomyoma and gastrointesinal stromal tumor. For more accurate diagnosis and treatment, minimally-invasive approaches may be suitable for the surgical enucleation of indicated esophageal submucosal tumor.
Adult ; Aged ; Esophageal Neoplasms/*pathology/*surgery/ultrasonography ; Esophagus/pathology ; Female ; Gastrointestinal Stromal Tumors/diagnosis/surgery ; Humans ; Intestinal Mucosa/*pathology ; Leiomyoma/diagnosis/surgery ; Male ; Middle Aged ; Retrospective Studies ; Thoracoscopy

BACKGROUND/AIMS: The accurate preoperative prediction of the risk of malignancy of gastrointestinal stromal tumors (GISTs) is difficult. The aim of this study was to determine whether tumor size and endoscopic ultrasonography (EUS) features can preoperatively predict the risk of malignancy of medium-sized gastric GISTs. METHODS: Surgically resected, 2 to 5 cm gastric GIST patients were enrolled and retrospectively reviewed. EUS features, such as heterogeneity, hyperechoic foci, calcification, cystic change, hypoechoic foci, lobulation, and ulceration, were evaluated. Tumors were grouped in 1 cm intervals. The correlations of tumor size or EUS features with the risk of malignancy were evaluated. RESULTS: A total of 75 patients were enrolled. The mean tumor size was 3.43+/-0.92 cm. Regarding the risk of malignancy, 51 tumors (68%) had a very low risk, and 24 tumors (32%) had a moderate risk. When the tumors were divided into three groups in 1 cm intervals, the proportions of tumors with a moderate risk were not different between the groups. The preoperative EUS features also did not differ between the very low risk and the moderate risk groups. CONCLUSIONS: Tumor size and EUS features cannot be used to preoperatively predict the risk of malignancy of medium-sized gastric GISTs. A preoperative diagnostic modality for predicting risk of malignancy is necessary to prevent the overtreatment of GISTs with a low risk of malignancy.
Aged ; *Endosonography ; Female ; Gastrointestinal Stromal Tumors/*pathology/surgery/*ultrasonography ; Humans ; Male ; Middle Aged ; Mitotic Index ; Predictive Value of Tests ; Preoperative Period ; Retrospective Studies ; Risk Assessment ; Stomach Neoplasms/*pathology/surgery/*ultrasonography ; Tumor Burden

Some special types of stomach tumors are often encountered in clinical paractice, such as gastrointestinal stromal tumor (GIST), gastric neuroendocrine tumors (NETs), primary gastric lymphoma (PGL) and some special types of gastric cancer. Because of their special pathogenesis and pathological types with lower incidence, the choices of the treatment for these diseases are limited. This article analyzes these special types of stomach tumors in order to improve the understanding of doctors in these diseases.
Gastrointestinal Stromal Tumors ; pathology ; surgery ; Humans ; Lymphoma ; pathology ; surgery ; Neuroendocrine Tumors ; pathology ; surgery ; Stomach Neoplasms ; pathology ; surgery