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Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P>0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population (P<0.01), imatinib treatment group (P=0.044) and no imatinib treatment group (P<0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS (P=0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.
Subject(s)
Male , Female , Humans , Middle Aged , Gastrointestinal Stromal Tumors/surgery , Retrospective Studies , Antineoplastic Agents/therapeutic use , Prognosis , Imatinib Mesylate/therapeutic use , Mutation , Proto-Oncogene Proteins c-kit/geneticsABSTRACT
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.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Gastrointestinal Stromal Tumors/pathology , Retrospective Studies , Clinical Relevance , Imatinib Mesylate , Biopsy , S100 ProteinsABSTRACT
Objective:To explore the mechanism of EV71 antagonizing IFN signaling pathway.Methods: RD cells were infected or un-infected with EV71.Then the cells were treated with or without IFN-β.The four groups (the control group,the EV71 group,the IFN-β group,the EV71+IFN-β group) were detected by molecular biology techniques.The expression of interferon stimulated genes (ISGs) were detected by Real-time PCR,while the protein levels of STAT1 and IRF9 were examined by Western blot assay.By preparing the cytosolic and nuclear fractions,the translocation of p-STAT1 was monitored through Western blot assay.Results:Compared with the IFN-β group,the mRNA level of OAS1,MX1 and ISG54 in the EV71+IFN-β group was down regulated by 47%, 50% and 48%,respectively,indicating that EV71 inhibited the expression of ISGs.The results also showed that EV71 did not effect the protein level and phosphorylation of STAT1.Moreover,we found that p-STAT1 was translocated into neuclear in IFN-β group,while p-STAT1 was located in the cytoplasm in the EV71+IFN-β group.And the expression of IRF9 was boviously down regulated in EV71+IFN-β group compared with that in IFN-β group,suggesting that EV71 blocked the expression of IRF9 induced by IFN-β.Conclusion:EV71 inhibited the IFN signaling pathway by downregulating the expression of IRF9 induced by IFN-β.
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BACKGROUND: The treatment of degenerative knee osteoarthritis is mainly to relieve pain, restore knee function, improve quality of life, delay knee replacement, and reduce the number of revisions. Knee replacement is currently the most common treatment for this disease, but it costs much, has great trauma and high risk, often results in prosthesis loosening and peripheral infection, and has many adverse reactions. OBJECTIVE: We hypothesize that knee-preserving arthroscopic debridement for treatment of knee degenerative osteoarthritis in the elderly patients costs less, is effective, safe, and reliable. METHODS: A total of 212 elderly patients (knees) with degenerative knee osteoarthritis who receive treatment in the Second Hospital of Chaoyang (Liaoning Province, China) will be included in this study. These patients will be assigned to two groups according to patient's conditions and wishes (n = 106/group). In the control group, intra-articular injection of sodium hyaluronate will be performed, followed by oral administration of non-steroidal anti-inflammatory drugs, conventional physiotherapy, and quadriceps functional exercise. In the arthroscopic debridement group, arthroscopic debridement will be performed followed by oral administration of non-steroidal anti-inflammatory drugs, conventional physiotherapy, and quadriceps functional exercise. All patients will be followed up for 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years. RESULTS AND CONCLUSION: The primary outcome measure is the percentage of the number of patients with Hospital for Special Surgery (HSS) knee score ≥ 85 points at 2 years after surgery, which will be used to evaluate knee function recovery. The secondary outcome measures are the percentage of the number of patients with HSS knee score ≥ 85 points before surgery, 1 week, 1 month, 3 months, 6 months, and 1 year after surgery; HSS score, Visual Analogue Scale (VAS) score, The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee range of motion, hospitalization costs, and knee X-ray morphology before surgery, 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after surgery, medical costs after 2 years of treatment, incidence of adverse reactions at 1 week, 1 month, 3 months, 6 months, 1 year and 2 years after surgery. Findings from this study will reveal whether arthroscopic debridement for the treatment of degenerative knee osteoarthritis in the elderly patients has advantages of less adverse reactions, low treatment costs, and can effectively restore knee function. This trial has been approved by the Second Hospital of Chaoyang, Liaoning Province, China (approval number:2017-08-01).All protocols will be in accordance with Declaration of Helsinki,formulated by the World Medical Association.Written informed consent will be provided by participants. This trial was designed in June 2017. The recruitment of subjects and data collection will begin in June 2018. The recruitment of subjects will be finished in December 2018. Outcome measures will be analyzed in June 2021. This trial will be completed in August 2021. The results of the trial will be reported in a scientific conference or disseminated in a peer-reviewed journal. This trial had been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800015208). The version of this study protocol is (1.0).
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Objective: To observe the effect of subarachnoid nerve block anesthesia on glutamate transporter glutamate-aspartate transporter (GLAST) and GLT-1 expressions in rabbits, and to investigate the effect of peripheral nerve anesthesia on the morphology and function of the spinal cord. Methods: Twenty healthy New Zealand white rabbits were randomly divided into two groups: the experimental group and control group; with 10 rabbits in each group. For spinal nerve anesthesia, 5 g/L of bupivacaine was used in the experimental group, and sterile saline was used in the control group. After 30 min of cardiac perfusion, GLAST and GLT-1 protein expression in spinal neurons were detected by immunohistochemistry and immunofluorescence staining. Results: GLAST and GLT-1 protein-positive cells increased in neurons in the experimental group, compared with the control group (P < 0.05). Conclusions: After subarachnoid nerve block anesthesia, rabbit glutamate transporter GLAST and GLT-1 expression is increased; and spinal cord nerve cell function is inhibited.
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OBJECTIVE@#To observe the effect of subarachnoid nerve block anesthesia on glutamate transporter glutamate-aspartate transporter (GLAST) and GLT-1 expressions in rabbits, and to investigate the effect of peripheral nerve anesthesia on the morphology and function of the spinal cord.@*METHODS@#Twenty healthy New Zealand white rabbits were randomly divided into two groups: the experimental group and control group; with 10 rabbits in each group. For spinal nerve anesthesia, 5 g/L of bupivacaine was used in the experimental group, and sterile saline was used in the control group. After 30 min of cardiac perfusion, GLAST and GLT-1 protein expression in spinal neurons were detected by immunohistochemistry and immunofluorescence staining.@*RESULTS@#GLAST and GLT-1 protein-positive cells increased in neurons in the experimental group, compared with the control group (P < 0.05).@*CONCLUSIONS@#After subarachnoid nerve block anesthesia, rabbit glutamate transporter GLAST and GLT-1 expression is increased; and spinal cord nerve cell function is inhibited.