Objective To detective KRAS and BRAF mutations in gastrointestinal stromal tumors (GISTs) and explore its significance in resistance of imatinib treatment. Methods Three hundred and eighty-one c-kit/PDGFRA mutation samples, 119 c-kit/PDGFRA wild type samples, and 19 pairs of samples before and after imatinib resistance from 519 patients with GIST were enrolled in this study. Polymerase chain reaction was used to detect KRAS exon 2 and BRAF exon 15 mutations. The survival data were evaluated in patients with KRAS or BRAF mutation. Results KRAS mutation was found in 2 cases (1.7%) of c-kit /PDGFRA wild type GISTs, the type of KRAS mutation was G12D and G12C, respectively. BRAFV600E mutation was found in 2 cases (1.7%) of wild type GISTs. No KRAS and BRAF mutations were found in the patients with the c-kit/PDGFRA mutation GISTs and pairs of GISTs before and after imatinib resistance. Two patients with KRAS mutation showed shorter progression free survivals for imatinib treatment. Two patients with BRAF mutation had longer recurrence free survivals. Conclusions Low frequency of KRAS or BRAF mutation only happens in wild type GISTs. KRAS mutation might be related to imatinib primary resistance, but not to secondary resistance.
Objective To analyze features of color Doppler ultrasonography in gastrointestinal stromal tumors. Method The ultrasound images of gastrointestinal stromal tumors (51 cases) and gastrointestinal cancers (59 cases) confirmed by operation and pathology were compared and analyzed. Results The gastric stromal tumor mainly occurred at the bottom of the stomach and the body of the stomach (17 cases), the intestinal stromal tumor mainly occurred at the small intestine (24 cases). The gastric cancer mainly occurred at the gastric antrum (18 cases), the intestinal cancer all occurred at the colon (20 cases) and rectum (12 cases). Compared with the gastrointestinal cancers, the gastrointestinal cavity was not surrounded by tumor, the peripheral boundary was clear, the morphology was more regular, the internal echo was uneven, and there was no peripheral lymph node metastasis in the gastrointestinal stromal tumors, the differences were statistically significant (P<0.05). There were no significant differences in the degree of blood flow and tumor diameter between the gastrointestinal stromal tumors and the gastrointestinal cancers (P>0.05), but the blood flow of the intestinal stromal tumor was significantly more abundant as compared with the intestinal cancer (P<0.05). Conclusion Color Doppler ultrasonography, as a simple and rapid method, has a certain diagnostic value for differentiation of gastrointestinal stromal tumors and gastrointestinal cancers.
ObjectiveTo summarize current treatment methods and research advances of liver metastasis in patients with gastrointestinal stromal tumor (GIST).MethodThe related literatures about treatment of liver metastasis in patients with GIST were collected and reviewed.ResultsGIST often occurred liver metastasis, which seriously affected the prognosis of patients. In the era of tyrosine kinase inhibitors (TKI) treatment, radical resection combined with TKI was the first choice. In addition, radiofrequency ablation and interventional therapy could be selected according to the patient’s condition.ConclusionsComplete resection of tumor and TKI treatment can improve the prognosis and survival rate of GIST patients with liver metastasis. GIST patients with liver metastasis need multi-disciplinary and multi-mode combined treatment.
Objective To summarize progress on diagnosis and treatment of advanced gastrointestinal stromal tumor (GIST). Method Through the retrieval of relevant literatures, the advances in the diagnosis and treatment of advanced GIST in recent years were reviewed. Results The diagnosis of advanced GIST mainly depends on imaging examination such as CT, MRI and endoscopy or endoscopic ultrasound. The diagnosis can be confirmed by needle biopsy for advanced GIST patients considering preoperative imatinib treatment. At present, the imatinib is the first-line therapy for patients with advanced GIST, followed by sunitinib and other novel targeted drugs. A multidisciplinary treatment strategy that included targeted therapeutic agents, combining with surgical resection, radiofrequency ablation and embolism chemotherapy have brought dramatic clinical benefit for advanced GIST. Conclusions GIST is easy to metastasis, clinicians should ensure early diagnosis and early treatment. In course of imatinib treatment, an individualized therapeutic regimen should be applied to treat advanced GIST based on specific situation of patients.
Carney triad is a rare tumor syndrome with few reports. This case showed the enhanced CT and MRI images of a rare young woman patient with Carney triad (containing gastric stromal tumor, renal cell carcinoma, adrenal pheochromocytoma, and pulmonary chondrosarcoma), which is intended to provide a reference for clinical diagnosis and differential diagnosis. This case reminds the radiologists and clinicians that the patients with a history of primary gastrointestinal stromal tumor and neoplastic lesions occurring at specific sites (pulmonary chondrosarcoma, adrenal pheochromocytoma, renal cell carcinoma, etc.) need to be alerted to the possibility of combining with Carney triad.
ObjectiveTo analyze the relevant risk factors affecting postoperative relapse-free survival (RFS) in the primary gastrointestinal stromal tumors (GIST) and develop a Nomogram predictive model of postoperative RFS for the GIST patients. MethodsThe patients diagnosed with GIST by postoperative pathology from January 2011 to December 2020 at the First Hospital of Lanzhou University and Gansu Provincial People’s Hospital were collected, and then were randomly divided into a training set and a validation set at a ratio of 7∶3 using R software function. The univariate and multivariate Cox regression analysis were used to identify the risk factors affecting the RFS for the GIST patients after surgery, and then based on this, the Nomogram predictive model was constructed to predict the probability of RFS at 3- and 5-year after surgery for the patients with GIST. The effectiveness of the Nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), consistency index (C-index), and calibration curve, and the clinical utility of the Nomogram and the modified National Institutes of Health (M-NIH) classification standard was evaluated using the decision curve analysis (DCA). ResultsA total of 454 patients were included, including 317 in the training set and 137 in the validation set. The results of multivariate Cox regression analysis showed that the tumor location, tumor size, differentiation degree, American Joint Committee onCancer TNM stage, mitotic rate, CD34 expression, treatment method, number of lymph node detection, and targeted drug treatment time were the influencing factors of postoperative RFS for the GIST patients (P<0.05). The Nomogram predictive model was constructed based on the influencing factors. The C-index of the Nomogram in the training set and validation set were 0.731 [95%CI (0.679, 0.783)] and 0.685 [95%CI (0.647, 0.722)], respectively. The AUC (95%CI) of distinguishing the RFS at 3- and 5-year after surgery were 0.764 (0.681, 0.846) and 0.724 (0.661, 0.787) in the training set and 0.749 (0.625, 0.872) and 0.739 (0.647, 0.832) in the validation set, respectively. The calibration curve results showed that a good consistency of the 3-year and 5-year recurrence free survival rates between the predicted results and the actual results in the training set, while which was slightly poor in the validation set. There was a higher net benefit for the 3-year recurrence free survival rate after GIST surgery when the threshold probability range was 0.19 to 0.57. When the threshold probability range was 0.44 to 0.83, there was a higher net benefit for the 5-year recurrence free survival rate after GIST surgery. And within the threshold probability ranges, the net benefit of the Nomogram was better than the M-NIH classification system at the corresponding threshold probability. ConclusionsThe results of this study suggest that the patients with GIST located in the other sites (mainly including the esophagus, duodenum, and retroperitoneum), with tumor size greater than 5 cm, poor or undifferentiated differentiation, mitotic rate lower than 5/50 HPF, negative CD34 expression, ablation treatment, number of lymph nodes detected more than 4, and targeted drug treatment time less than 3 months need to closely pay attentions to the postoperative recurrence. The discrimination and clinical applicability of the Nomogram predictive model are good.
ObjectiveTo detect expressions of E-cadherin (E-cad) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST) tissues and analyze their relationships with clinicopathologic features of patients with GIST.MethodsForty paraffin-embeded specimens of surgical resected GIST from January 2015 to March 2018 in the Pathology Department of Yuhuangding Hospital Affilicated to Qingdao University were retrieved. The expressions of E-cad and VEGF proteins were detected by the immunohistochemical method.ResultsThe positive expression rates of E-cad and VEGF proteins in the GIST tissues were 10.0% (4/40) and 50.0% (20/40), respectively. The positive expression rates of E-cad and VEGF proteins were associated with the tumor diameter, mitotic counts, and risk classification (P<0.05). The positive expression rate of the E-cad was negatively related to that of the VEGF in the GIST tissues (rs=–0.55, P=0.001).ConclusionFrom results of this study, VEGF and E-cad might be related with malignancy of GIST, which might be potential facators in predicting prognosis of GIST.
Objective To describe pharmacokinetic of imatinib in a cohort of gastrointestinal stromal tumor (GIST) patients in routine clinical care from West China Hospital of Sichuan University. Methods The imatinib trough concentration (Cmin) in 42 patients with GIST who were taking imatinib in routine clinical care setting in West China Hospital from 2010 to 2016 was measured. The clinical features and follow-up data were collected. Results The mean imatinib Cmin in 42 patients was 1 757 μg/L (199–7 435 μg/L), 10 of 42 patients presented with Cmin values was lower than 1 000 μg/L. The imatinib Cmin of 18 patients received an imatinib dose of 300 mg/d or 24 patients treated with 400 mg/d imatinib was (1 313±479) μg/L and (1 775±1 520) μg/L, respectively (P=0.222), but the rate of low Cmin (lower than 1 000 μg/L) in the two different dose groups had no significant difference (P=0.347). In Cox regression, no statistically significant association between the low Cmin and the time to progression of GIST could be demonstrated 〔HR=0.171, 95%CI：(0.106, 12.990),P=0.898〕. Conclusion The preliminary results of limited cases in this study show that some GIST patients are systematically underexposed in routine clinical care, an individualized treatment based on monitoring of imatinib Cmin is likely to be more efficient than a fixed-dose treatment.
Objective To investigate the correlation between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune inflammation index (SII) and clinicopathological characteristics and prognosis in patients with gastrointestinal stromal tumor (GIST). Methods The clinicopathological data and blood routine results of 101 patients with GIST who were treated surgically in the General Hospital Western Theater Command PLA from December 2014 to December 2018 were collected retrospectively, samples were obtained to calculate NLR, PLR and SII. The optimal cutoff value of NLR, PLR and SII were evaluated by receiver operating characteristic (ROC) curve. The Chi-square test and t-test were used to analyze the relationship between NLR, PLR, SII and clinicopathological characteristics of GIST. The Kaplan-Meier plots and the log-rank test were used to analyze the influence factors affecting the recurrence-free survival (RFS) of patients with GIST. Multivariate Cox regression analyses was used to identify the independent influence factors affecting the RFS of patients with GIST. Results The preoperative peripheral blood NLR, PLR and SII of patients with GIST were correlated with the tumor site, tumor diameter and modified NIH risk stratification (P<0.05), but not with the mitotic count of tumor cells (P>0.05). Kaplan-Meier plots and log-rank test showed that NLR, PLR, SII, surgical method, tumor site, tumor diameter, mitosis rate and modified NIH risk stratification were the influential factors of RFS in with GIST. The multivariate Cox regression analysis revealed that postoperative whether to accept regular imatinib adjuvant therapy (HR=32.876, P<0.001), modified NIH risk stratification (HR=129.182, P<0.001), and PLR (HR=5.719, P=0.028) were independent influence factors affecting the RFS of patients with GIST. Conclusions Preoperative peripheral blood PLR, NLR, and SII are correlated with clinicopathological characteristics such as the tumor location, tumor diameter and modified NIH risk stratification, and are the influencing factors of postoperative RFS in patients with GIST. PLR is an independent predictor of RFS in patients with GIST.
ObjectiveThis review has summarized in detail the advances in computed tomography (CT) and magnetic resonance imaging (MRI) imaging in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST).MethodsTo summarize the image-related guidelines, consensus, international conference reports, and relevant knowledge of clinical research on the evaluation of the efficacy of GIST targeted therapy in recent years.ResultsThe CT and MRI manifestation after targeted treatment of GIST was closely related to pathological changes, including necrosis, cystic degeneration, and bleeding. CT was the preferred imaging method. Functional magnetic resonance imaging, such as diffusion weighted imaging (DWI), had made some progress. The main criteria for evaluating the efficacy of GIST targeted therapy were RECIST 1.1 and Choi criteria.ConclusionCT and MRI play an important role in evaluating the efficacy of targeted therapy for GIST.