[Abstract Objective clinical features of gastrointestinal stromal tumors (GISTs), treatment and prognosis. Confirmed by pathology at the Beijing Union Medical College Hospital from 1986 to January 2006, all patients with gastrointestinal stromal tumors clinical manifestations, diagnosis, treatment, and prognosis were retrospectively analyzed. Results A total of 91 patients diagnosed with gastrointestinal stromal tumors. Mainly originated in the stomach (35 cases, 38.5%) and small intestine (30 cases, 33.0%). 68 cases (75%) had clinical symptoms, the most common clinical manifestations of abdominal pain, gastrointestinal bleeding, weight loss. Endoscopy and CT diagnosis of gastrointestinal stromal tumor is more important, the positive rate of over 90%. Immunohistochemical CD117-positive rate of 83.7%, 88.5% of CD34 positive rate. Treatment with surgery, lymph node metastasis (3.3%) occurred rarely. Seven patients with advanced GISTs line-line chemotherapy, were invalid. 11 patients with advanced GISTs line imatinib therapy, 10 patients to evaluate the efficiency of 40% and 80% of the clinical benefit rate; median survival time has reached 10 months. Long term follow up of 91 cases in 84 cases, the median followed up 13 months, with a median survival time of 16.5 months, 1-year survival rate was 52.9%, 2-year survival rate was 19.5%. Conclusion gastrointestinal stromal tumor clinical features different from other common gastrointestinal tumors, CD117 their diagnosis is important, molecularly targeted therapy prolongs survival in patients with advanced GISTs.
Key words stromal tumors in the gastrointestinal tract, the clinical features of the treatment of pre-Houyi Ma erlotinib
Gastrointestinal stromal tumors (Gastrointestinal stromal tumors, GISTs) is a rare gastrointestinal tumors, gastrointestinal stromal stem cells independent origin, its clinical manifestations, treatment and prognosis is different from the other common tumors of the gastrointestinal tract. The Beijing Union Medical College Hospital from 1986 to January 2006, 20 years, all diagnosed with gastrointestinal stromal tumor patients with clinical features, diagnosis, treatment and prognosis were retrospectively analyzed.
1 objects and methods
1.1 The study from 1986 to January 2006 at the Beijing Union Medical College Hospital pathologically confirmed in all patients with gastrointestinal stromal tumors.
1.2 Methods A retrospective analysis of eligible patients, clinical manifestations, diagnosis, treatment, prognosis summary analysis.
1.3 statistical methods using SPSS 10.0 statistical software.
2.1 General Information Since 1986 to January 2006, the Beijing Union Medical College Hospital were treated 91 cases of gastrointestinal stromal tumors. There were 48 males and 43 females, male: female = 1.1:1. Age 20 to 84 years, with an average age of 55.2 years, with a median age of 58 years old.
2.2 Clinical manifestations of 68 cases (75%) had clinical symptoms, the most common clinical manifestations of 31 cases (34%), followed by 25 cases of gastrointestinal bleeding (27%), weight loss in 15 cases (16%) were abdominal pain, abdominal discomfort five cases (5.5%), fever in 5 cases (5.5%), intestinal obstruction in 5 cases (5.5%), gastrointestinal perforation in 3 cases (3.3%). 23 cases (25%) patients with no obvious symptoms, tumor stumbled on self-examination or physical examination.
The 2.3 auxiliary examination of the stomach gastrointestinal stromal rumen mirror found abnormal ratio (24/25 patients (96%) of the positive rate), ultrasound gastroscope positive rate of 11/11 cases (100%), upper gastrointestinal contrast positive rate of 13 / 15 cases (87%), abdominal CT-positive rate of 21/21 cases (100%), abdominal B-positive rate of 12/24 cases (50%). Between the small stomach intestinal the stromal tumors enteroscopy positive rate 3/3 (100%), capsule endoscopy positive rate of 4/4 (100%), small bowel contrast positive rate of 2/3 of the patients (67%), common digestive tract The the contrast positive rate of 5/11 patients (45%), abdominal pelvic CT-positive rate of 14/18 cases (78%), the abdominal pelvic B-positive rate of 15/25 cases (60%). The group of gastrointestinal stromal tumors CT overall positive rate of 49/54 cases (91%). Endoscopic biopsy pathology positive rate is low, 1/17 patients (6%) were diagnosed with suspected 4/17 cases (24%), negative 12/17 cases (70%). The pathological positive rate of CT-guided tumor puncture 4/4 (100%).
The site of origin of the 2.4 tumor characteristics (1): 91 cases of gastric origin of 35 cases (38.5%), including two cases of the stomach at the same time found that the two lesions; small intestine of 30 cases (33.0%), including one case of multiple isolated lesions found in the small intestine ; stomach and pancreas duodenum and the origin of one cases (1.1%); rectum in 8 patients (8.8%); mesangial 7 cases (7.7%); colon in 2 cases (2.2%); esophagus in 1 case (1.1%); 1 case (1.1%); the peritoneal one cases (1.1%); retroperitoneal 1 case (1.1%); unknown four cases (4.4%). (2) the merger of the second tumor: eight cases (8.8%) concomitant tumor, 6 patients with other gastrointestinal tumors, the other two cases were consolidated adrenal and ovarian tumors; merger of the second tumor in three cases endocrine tumors, three cases of adenocarcinoma. (3) Size: tumor size 0.3 to 35cm <5cm in 27 cases, ≥ 5cm and <10cm in 29 cases, ≥ 10cm and <20cm in 14 cases, ≥ 20cm in 8 cases, 13 cases size is unknown. (4) immunohistochemistry: CD117 positive rate of 83.7% (72/86 cases), CD34 positive rate of 88.5% (69/78 cases); 77 cases of simultaneous detection of CD117, CD34, were positive in 59 cases (76.6%) were negative for the three cases (3.9%). (5) the degree of malignancy: malignant 60 cases of potentially malignant five cases, 26 cases of benign and malignant unknown. Which a total of nine cases of gastrointestinal stromal tumors are malignant.
The 2.5 staging patients with 91 cases of GISTs diagnosis, node-positive cases, nine cases of distant metastasis. Distant metastatic sites: liver metastases in 6 cases, peritoneal mesangial the omental transfer of five cases.
2.6 initial treatment of 87 cases and four cases of retreatment. Surgery: 91 cases, 88 patients underwent surgery. 32 routine lymph node dissection (pathologically confirmed), only 3 patients (9.4%), positive lymph nodes; 1 to 15 the number of lymph node dissection, an average of 5.3, with a median of four. Rescue treatment: 7 patients with advanced GISTs line first-line chemotherapy, treatment 2 to 4, the efficacy assessment were disease progression (100%). 11 patients with advanced GISTs line imatinib therapy, medication for 0.5 to 19 months, an average of 9.0 months, with a median of four months; 1 cases impossible to assess the short time for medication, 10 patients evaluable, one cases of complete remission ( 10%), partial remission in 3 cases (30%), stable in 4 patients (40%), progress in 2 cases (20%), clinical benefit rate of 80%; median survival time has reached 10 months.
2.7 prognosis (1) All cases were followed up until March 1, 2006, of which seven cases were lost. Were followed up for 2 to 221 months, and the median followed up 13 months. 84 cases, nine cases have died, including six cases died within 1 year, 2 patients died within 1 year and not more than 2 years and another patient died when five years. (2) the median survival time of 16.5 months. 1-year survival rate was 52.9%, the 2-year survival rate was 19.5%. The survival curves shown in Figure 1.
Figure 1 gastrointestinal stromal tumor patient survival curves
Mazur and Clark in 1983  will be named after a special class of gastrointestinal mesenchymal tumors of gastrointestinal stromal tumors, in the 1980s, these tumors are often divided into leiomyoma (or sarcoma ) or neurofibromas (or sarcoma).
Our hospital in 2001 confirmed the first case of gastrointestinal stromal tumor, began the understanding of these diseases, the diagnosis of the number of cases increased year by year. 91 cases and four cases previously diagnosed as leiomyosarcoma diagnosed with gastrointestinal stromal tumor recurrence and metastasis, as shown in Table 1. Gastrointestinal stromal tumor is a rare tumor, but because of the inadequate understanding of the disease, resulting in some cases of misdiagnosis. Beijing Union Medical College Hospital from 2004 to 2005 for 2 years the diagnosis of 65 cases of gastrointestinal stromal tumors, accounting for the same period to 2.55% of gastrointestinal malignancies treated.
This article GISTs no significant gender differences, with a median age of 58 years old, the minimum age is 20 years old, maximum 84 years, 40 years of age and 9 patients (10%). [2,3] is consistent with the large-scale epidemiological findings.
This paper 91 cases of GISTs, primary in the stomach (38.5%), followed by the small intestine, 33.0% to 8.8% in third place rectum, colon, esophagus, pancreas were distributing, and another 10% originated in the gastrointestinal omentum Table 1 past diagnosis for patients with leiomyosarcoma list
Previous the GIST diagnosis of patients 11995 stomach tumor resection, the diagnosis of leiomyosarcoma
1999 gastric tumor resection, diagnosis of leiomyosarcoma recurrence 2004 gastrectomy and intra-abdominal tumor resection, the diagnosis of gastric tumor resection of the the GIST cases of 21,985 years, the diagnosis of leiomyosarcoma
Right lobe resection in 1998, the diagnosis of epithelioid leiomyosarcoma metastatic liver cancer in 2003 resection to diagnose the GIST cases of 32,000 rectal tumor resection, the diagnosis of leiomyosarcoma 2003 laparotomy and found that liver and rectal wall tumor biopsy the GIST cases of 41,997 years of small bowel tumor resection, liver biopsy diagnosis of leiomyosarcoma 2004, diagnosis of GIST
Mesenteric or retroperitoneal. The the reported primary in the stomach about 50% to 60%, small intestine 25% to 30%, rectum, esophagus 2%, other abdominal organs (such as the appendix, gallbladder, pancreas and omentum) 5% [4-6 ]. Compared with the literature, this paper stomach origin low proportion of small intestine is slightly higher; mainly considering the small number of cases derived from a single center, may also be associated with racial differences.
This article 75% of GISTs patients with clinical symptoms, common complaints were abdominal pain, gastrointestinal bleeding, weight loss, 5.5% of patients with fever. Another 25% of patients with no apparent conscious discomfort. As can be seen, no specific clinical manifestations of gastrointestinal stromal tumors. According to the bulk of clinical cases reported (1765 cases), 54.4% of patients first performance for anemia caused by gastrointestinal bleeding, vomiting blood or black stools, 16.8% of the patients showed upper abdominal pain and discomfort, 1.7% of patients with symptoms of acute abdomen [3,4].
GISTs onset occult, the nonspecific imaging studies, early diagnosis is difficult. Gastrointestinal barium meal of GISTs diagnosis and site-related gastric maximum of 87%, while less than 50% of the small intestinal GISTs positive rate from the data analysis. CT diagnosis of GISTs sensitive than barium meal, the overall positive rate of 91%. Endoscopic highest positive rate of 96% to 100%. Reported in the literature, barium meal gastric stromal tumors mainly local mucosal folds flatten or disappear, and no apparent stomach the cavity narrows performance; small intestinal stromal tumors have different degrees of intestinal mucosa limitations disappear, destruction, involving only the side of the intestinal wall, and development along the long axis of the intestine, causing the narrow intestine laterality, this change has a certain diagnosis [7,8].
Due to the GISTs lesions located muscularis preoperative pathological diagnosis more difficult. This paper 17 cases of endoscopic biopsy positive rate was only 6% for biopsy-negative cases, can not completely rule out the possibility of GISTs. The pathological positive rate of CT-guided tumor puncture higher in our hospital to puncture four cases, four cases were positive.
GISTs immune phenotype unique CD117 is a specific marker of GISTs positive rate of 85% to 94%, generally showed strong diffuse cytoplasmic staining; CD34 positive expression in 60% to 70% of GISTs ; of GISTs Unlike leiomyomas or schwannomas, myogenic or neurogenic immune marker expression was lower, according to statistics, SMA-positive rate of 30% to 40% of Desmin and S-100 expression were less than 5%. Our hospital diagnosed 91 cases of GISTs, CD117-positive rate of 83.7%, CD34 positive rate of 88.5%. CD117 critical to the diagnosis of GISTs, but be sure to reference morphologic features, and the CD117 negative can not be completely rule out the possibility of GISTs.
The early years, in accordance with the the Lewin standard (1992) , GISTs divided into three categories: (1) malignant: histologically confirmed metastasis or infiltration into adjacent organs; (2) malignant potential: (1) gastric tumors> 5.5 cm , intestinal tumors> 4 cm; ② mitotic stomach tumors> 5/50 the HPF intestinal tumors> 1/50 the HPF; ③ tumor necrosis; ④ nuclear atypia; ⑤ tumor cells rich active growth; ⑥ epithelioid cells were nested or alveolar; (3): do not have the above-mentioned indicators for benign benign. According to statistics, when diagnosed GISTs from 10% to 30% belongs to the vicious, the potentially malignant accounted for 70% to 90% , may have malignant over time. Therefore not really benign gastrointestinal stromal tumors, described as low grade and high grade more exact. The GISTs prognosis depends on the size of the tumor cells in the mitotic index, depth of tumor invasion and metastasis.
The GISTs growth characteristics pendant, rather than invasive growth. GISTs patients with few lymph node metastases, 91 patients of this article is only three cases of pathologically confirmed lymph node metastasis, lymph node metastasis only 3.3%. The GISTs transfer to the liver is the most common (54% to 65%), followed by peritoneal (20% to 21%), bone (6%) and lung (2%). Article 91 cases of GISTs in patients with liver metastases occurred in 16 patients (17.6%), the peritoneal 13 cases (14.3%), lung metastases in 4 patients (4.4%), brain metastasis in 3 cases (3.3%), adrenal metastasis in 2 cases (2.2%) , boneless transfer. Distant metastasis rate is low compared with literature data, the analysis of the main reasons is followed up for a shorter time. Any case the GISTs this growth infiltration gastrointestinal epithelial cancer.
Surgical resection is the main treatment for GISTs patients , according to statistics, about 83% of patients can be radical resection, but 85% of patients after recurrence, metastasis , 5-year survival rate of only 50 65 %. And from 15% to 50% of patients for treatment at advanced stage, and lost opportunities for radical resection. Than 9.9% found in this article 91 patients were diagnosed with distant metastases. 88 cases of surgery, with a median followed up for 1 year, 17 patients (19.3%) had recurrence and metastasis.
GISTs are not sensitive to conventional radiation and chemotherapy, and less than 10% efficiency. Chemotherapy and radiotherapy for recurrence of GISTs almost no effect. This article 7 patients with advanced GISTs line first-line chemotherapy, the effective rate of 0.
Found GISTs with Kit kinase gene mutations, imatinib (Gleevec) is a molecular target for drugs against c-Kit gene product. Phase III clinical studies have shown that the application of the treatment of advanced imatinib of GISTs remission rate of 48% to 53%, disease control rate of approximately 80% [12, 13]; patients with good response, with a median survival of about 20 ~ 24 months [2,4]. Herein 11 patients with advanced GISTs line imatinib therapy, 10 patients evaluable efficiency of 40%, including complete remission (10%), clinical benefit rate of 80%; median survival time has reached 10 months.
In recent years, with the development of molecular biology and the use of imatinib, deepening understanding of GISTs. We will also continue the case the GISTs of patients followed up in our hospital, and to improve the diagnosis and treatment of this disease, a better understanding of this disease.