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*

Objective: To investigate the clinical significance of pathological diagnosis and genetic abnormalities detection of gastrointestinal stromal tumor (GIST) using endoscopic biopsy. Methods: Patients with GIST diagnosed by endoscopic biopsy (from January 1st, 2016 to August 1st, 2018, at Zhongshan Hospital, Fudan University) were included in this study. This retrospective study evaluated the histopathologic and immunohistochemical (IHC) features, genetic abnormalities of the tumors and the treatment and clinical course of the patients. Results: Totally 4 095 cases of GIST were collected, among which 67 patients (67/4 095, 1.6%) underwent endoscopic biopsy. Forty-eight patients (71.6%) were male and 19 (28.4%) were female, with a mean age of 61 years (range 31-90 years). Fifty-nine lesions were located in stomach and eight in duodenum. Of all the 67 cases, 47 were spindle type, 14 were epithelioid type, and 6 mixed type. IHC staining showed the positive rates were 100.0% (64/64) for DOG1, 98.4% (62/63) for CD117, 87.5% (56/64) for CD34, 3.6% (2/56) for S-100 protein, 12.1% (7/58) for α-SMA, 12.3% (7/57) for desmin and 4.0% (2/50) for CKpan. Morphologically, 34 cases were malignant; three cases (all epithelioid type) were originally misdiagnosed as poorly differentiated carcinoma; missed-diagnosis were found in four cases (spindle type) due to the insufficient diagnostic tumor cells. The genetic abnormality detection rate in the biopsy tissue was 38.8% (26/67),among them two patients were lost to follow up after biopsy, 33 patients received surgical resection, 16 cases underwent operation after neoadjuvant therapy and 16 patients with advanced disease underwent continuous imatinib therapy, with the genetic testing rate of 6.1% (2/33), 10/16 and 14/16, respectively. Conclusions: Endoscopic biopsy is a useful but rare method for the preoperative diagnosis of GIST. For majority of biopsy, accurate pathological diagnosis and auxiliary examination can be completed to guide clinical treatment. A thorough history in combination with endoscopic finding is essential to avoid misdiagnosis (epithelioid type) and missed diagnosis (spindle type) in suspicious cases. Genetic testing should be recommended in patients who will undergo targeted therapy after endoscopic biopsy, and it can provide valuable information and guidance for clinical treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Gastrointestinal Stromal Tumors/pathology* ; Retrospective Studies ; Clinical Relevance ; Imatinib Mesylate ; Biopsy ; S100 Proteins

Gastrointestinal Stromal Tumors/pathology* ; Humans ; Proto-Oncogene Proteins c-kit/genetics*

Gastrointestinal Stromal Tumors/pathology* ; Heart Ventricles/pathology* ; Humans ; Liver Neoplasms ; Tomography, X-Ray Computed

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory disorder characterized by specific pathological findings and elevated serum IgG4 level. IgG4-RD in the stomach is rare, and occasionally diagnosed as gastric subepithelial tumor (SET) by endoscopy or computed tomography scan. Two female patients in the age group of 40–50 years were diagnosed with 4 cm sized gastric SET. One underwent laparoscopic gastric wedge resection. Another one had a history of subtotal gastrectomy for early gastric cancer and idiopathic thrombocytopenic purpura with oral steroids administration. She underwent a completion total gastrectomy with splenectomy for the gastric SET and ITP. The pathology showed storiform fibrosis, and IgG4 was positive in immunohistochemistry (IHC) stain. IgG4-RD is known as a medical disease that could be treated with oral steroids. The difficulty in preoperative diagnosis of the disease occasionally causes unnecessary gastric resection. Thus, preoperative diagnostic methods for IgG4-RD such as deep biopsy with IHC stain or magnetic resonance imaging are needed.
Biopsy ; Diagnosis ; Endoscopy ; Female ; Fibrosis ; Gastrectomy ; Gastrointestinal Stromal Tumors* ; Humans ; Immunoglobulin G ; Immunoglobulins ; Immunohistochemistry ; Magnetic Resonance Imaging ; Pathology ; Purpura, Thrombocytopenic, Idiopathic ; Splenectomy ; Steroids ; Stomach Neoplasms ; Stomach*

Management of large-size retrorectal gastrointestinal stromal tumors (GISTs) is complex and challenging from diagnosis to treatment. This may create technical difficulties in surgical access and complete resection of the tumor. The abdominosacral resection has the benefit of improved visualization via the anterior incision, with enhanced exposure of the midrectal area, which makes resecting the tumor completely via the posterior approach easier. We report 2 cases of patients with a retrorectal GIST and neurofibromatosis type 1, one in a 27-year-old woman with a defecation complaint and the other in a 58-year-old woman with a defecation and urination complaint. Based on the anatomical pathology, both patients were diagnosed with a GIST. The tumors were excised via an abdominosacral resection. Retrorectal GISTs are rare, and abdominosacral resection allows complete resection of a large-size retrorectal GIST with low morbidity and an absence of functional impairment. The abdominosacral resection should be considered in certain situations.
Adult ; Defecation ; Diagnosis ; Disease Management ; Female ; Gastrointestinal Stromal Tumors ; Humans ; Middle Aged ; Neurofibromatosis 1 ; Pathology ; Rectal Neoplasms ; Urination

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

Primary malignant small bowel tumor as a rare kind of intestinal tumor is associated with a poor prognosis. The pathological types were various and complicated, such as adenocarcinoma, neuroendocrine tumor, malignant lymphoma, and malignant stromal tumor. The atypical early stage symptom resulted in difficult diagnosis at early stage, high misdiagnosis rate and lack of standard therapy schemes and means. In the past, X-ray, CT, MRI, and PET-CT were the main examination methods for primary small bowel tumor. However, with the development of radiology, a series of new diagnosis methods, including electronic enteroscopy, capsule endoscopy, multi-slice spiral CT enteroclysis and so on, promotes the diagnosis accurate rate. Surgery is still the most important method in the small bowel tumor treatment, and the alternative of the surgical method should depend on the tumor location, size and relationship with the adjacent organs. Application of the laparoscopic surgery for the small bowel tumor is still in the initial stage. Besides, some researches have confirmed that chemotherapy, radiotherapy, target therapy and endocrinotherapy have effects on the specific kind of small bowel tumor. Therefore this article will review the epidemiology, pathology, diagnosis and treatment of the primary malignant small bowel tumors.
Adenocarcinoma ; diagnosis ; epidemiology ; pathology ; therapy ; Capsule Endoscopy ; Gastrointestinal Stromal Tumors ; diagnosis ; epidemiology ; pathology ; therapy ; Humans ; Intestinal Neoplasms ; diagnosis ; epidemiology ; pathology ; therapy ; Intestine, Small ; diagnostic imaging ; pathology ; Laparoscopy ; methods ; Lymphoma ; diagnosis ; epidemiology ; pathology ; therapy ; Neuroendocrine Tumors ; diagnosis ; epidemiology ; pathology ; therapy ; Tomography, Spiral Computed

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 clinical characteristics, diagnosis and treatment as well as prognostic factors of the giant gastrointestinal stromal tumor (GIST).

METHODSClinical data of 235 patients with high risk GIST treated in the Union Hospital, Tongi Medical College, Huazhong University of Science and Technology between January 2005 and July 2015 were retrospectively analyzed. Patients were divided into giant GIST group (diameter equal to or larger than 10 cm, 119 cases) and high risk group (diameter less than 10 cm, 116 cases) according to tumor size. Clinical characteristics and prognosis of two groups were compared and the clinical features of giant GIST were summarized. Multivariate analysis was performed to evaluate the prognostic factors of giant GIST with Cox regression model.

RESULTSOf the 119 patients with giant GIST, which accounted for 50.6%(119/235) of all the high risk patients, there were 63 male and 56 female patients with a median age of 53(20-82) years. Primary giant GIST of 43(36.1%) located in the stomach, of 39(32.8%) in the small intestine, 5(4.2%) in the colon and rectum, and of 32 (26.9%) outside the gastrointestinal tract (mesentery, retroperitoneum, abdominal cavity, etc) and pelvic. Compared to high risk group, age of onset was younger [ratio of ≤50 years, 44.5%(53/119) vs. 31.9%(37/116), P = 0.046] and incidence of outside the gastrointestinal tract was significantly higher [26.9%(32/119) vs. 9.5%(11/116), P=0.000] in giant GIST group. All the giant GIST patients underwent surgical resection, including 115 cases(96.6%) of R0 resection, 3 cases(2.5%) of R1 resection and 1 case(0.9%) of R2 resection, besides, 32 cases(26.9%) underwent expanded resection (namely, underwent lymphadenectomy or combined organ resection simultaneously). Thirty-nine giant GIST cases(32.8%)accepted imatinib 400 mg/d for targeted therapy after operations, which was not significantly different with high risk group (46 cases, 39.6%, P=0.232). Relapse and metastasis occurred in 8 cases in giant GIST group. The 1-, 3-, 5-year overall survival rates of giant GIST group were 94.5%, 89.3%, 79.4% respectively and of high risk group were 99.1%, 92.9%, 85.1% respectively, and no significant difference was found (P=0.788). The 1-, 3-, 5-year recurrence-free survival rates of giant GIST group were 93.6%, 85.1%, 72.8% respectively and of high risk group were 99.1%, 91.7%, 84.2% respectively, and no significant difference was found as well (P=0.932). Multivariate analysis revealed that gender (P=0.047, RR=0.383, 95%CI:0.149-0.987), mitotic count (P=0.001, RR=0.216, 95%CI:0.087-0.538) and targeted therapy(P=0.019, RR=5.719, 95%CI:1.324-24.695) were prognostic risk factors of overall survival (OS), moreover, tumor size (P=0.024, RR=0.368, 95%CI:0.155-0.875) and mitotic count(P=0.007, RR=0.357, 95%CI:0.169-0.755) were prognostic risk factors of RFS.

CONCLUSIONSGiant GIST is not unusual in GIST and more likely occurs outside gastrointestinal tract. Complete surgical excision combined with targeted therapy can improve the prognosis significantly. The prognosis of giant GIST and common high risk GIST is similar. Mitotic count is the most important prognostic factor.

Abdominal Cavity ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Female ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; drug therapy ; pathology ; Humans ; Imatinib Mesylate ; therapeutic use ; Intestine, Small ; Lymph Node Excision ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate ; Young Adult