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Lung cancer has the highest mortality rate in the world. The first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) greatly improve the survival time and quality of life of patients with non-small cell lung cancer (NSCLC) to some extent. However, after a period of progression-free survival, most patients develop drug resistance, in which T790M mutation is the mainly resistance mechanism. The third-generation EGFR-TKIs, represented by osimertinib, are found to have significant effect on this resistance. The effect is remarkable, but drug resistance is still inevitable. For example, C797S mutation, mesenchymal-epithelial transition (MET), RAS mutation, BRAF mutation, transformation of small cell lung cancer (SCLC), transformation of epithelial mesenchymal transition (EMT), etc. But, there is no standard and effective treatment after the third-generation EGFR-TKIs resistance. In this view, we summarize the research progress in the new generation EGFR-TKIs after third-generation, in order to provide some reference for the follow-up research and treatment. .
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Objective To evaluate the efficacy and survival rate of neoadjuvant chemotherapy with docetaxe and pirarubicin in triple negative breast cancer (TNBC).Methods Total 51 breast cancer patients were divided into TNBC group (n =26,including 16 of stage Ⅱ and 10 of stage Ⅲ patients) and non-TNBC group (n =25,including 14 of stage Ⅱ and 11 of stage Ⅲ patients).All patients received a median of 4 treatment cycles with TAC regimen [docetaxe 75 mg/m2 on day 1,pirarubicin 40 mg/m2 on day 1 and cyclophosphamide (CTX) 500 mg/m2 on day 1 of each 21 day cycle].The efficacy of treatment and survival rate of two groups were evaluated.Results In TNBC group,9 out of 26 (34.62 ％) patients achieved clinical complete response (cCR),and 14 (53.85 ％) had partial response (cPR).Overall,88.46 ％ of TNBC patients had clinical response and 26.92 ％ (7/26) showed pathology complete response (pCR).In non-TNBC group,6 (24.00 ％) patients reached cCR and 8 (32.00 ％) showed cPR.The overall response rate was of 56.00 ％,and 4 (16.00 ％) patients achieved pCR.The overall 3-year survival rates in TNBC and non-TNBC groups were 73.08 ％ and 88.00 ％,respectively,indicating a poorer prognosis of TNBC.The 5-year survival rates of TNBC patients with and without pCR were 88.89 ％ and 47.06 ％,respectively.Conclusion TAC regimen improves the prognosis for locally advanced TNBC,indicating that the neoadjuvant chemotherapy is effective and safe for TNBC patients.
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Objective To evaluate the effect of Shenfu Decoction pretreatment on the function of intestinal mucosal barrier of endotoxemic rats.Methods Twenty-four adult male Sprague-Dawley rats,aged 4-6 months,weighing 180-220 g,were randomly divided into 3 groups (n =8 each):blank control group (group C),endotoxemia group (group E) and Shenfu Decoction pretreatment group (group S).Endotoxemia was induced by lipopolysaccharide 10 mg/kg injected intravenously in anesthetized rats in groups E and S.Normal saline and Shenfu Decoction 5 ml/kg were injected intraperitoneally at 30 min before the model of endotoxemia was established in groups E and S,respectively.At 2 h after the model of endotoxemia was estabhshed,blood samples were obtained from the abdominal aorta for measurement of the plasma concentrations of tumor necrosis factor-α (TNF-α),interleukin6 (IL-6),intestinal fatty acid binding protein (i-FABP) and diamine oxidase (DAO) by ELISA.The distal ileum was harvested for detection of the expression of tight junctional protein Zonula Occludens-1 (ZO-1) in the intestinal mucosa of epithelial cells by immunohistochemistry.The changes in pathological morphology of the intestinal mucosa were examined after one segment of the distal ileum was stained with haematoxylin and eosin.The pathological changes were assessed and graded according to Chiu's score.Results Compared withgroup C,the plasma TNF-α,IL-6,i-FABP and D-lac concentrations were significantly increased,Chiu's scores were increased,and the expression of ZO-1 was down-regulated in groups E and S (P ＜ 0.05).Compared with group E,the plasma TNF-α and IL-6 concentrations were significantly decreased,the plasma i-FABP and D-lac concentrations were decreased,Chiu's scores were decreased,and the expression of ZO-1 was up-regulated in group S (P ＜ 0.05).Conclusion Shenfu Decoction pretreatment can attenuate the damage to the intestinal mucosa and protect the function of intestinal mucosal barrier in endotoxemic rats and inhibition of systemic inflammatory responses is involved in the mechanism.
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ObjectiveTo investigate the clinical value of transgastrie endoscopic surgery for the treatment of pancreatic abscess or pancreatic cyst and infection.MethodsThe clinical data of 22 patients with pancreatic abscess or pancreatic cyst and infection who underwent transgastric puncture and drainage or transgastric debridement under the guidance of endoscopic ultrasonography (EUS) at the Xinqiao Hospital of Third Military Medical University from July 2008 to August 2011 were retrospectively analyzed.All patients were comfirmed with bacteria infection after liquid aspiration culture. Patients with pancreatic abscess underwent endoscopic transgastric debridement,and for patients with pancreatic cyst and infection,10 F double pigtail stent and 8.5 F nasal bile duct were placed for drainage.ResultsThe results of liquid aspiration culture confirmed that 2 patients were infected by staphylococcus aureus,3 by proteus mirabilis,4 by pseudomonas aeruginosa,4 by klebsiella and 9 by escherichia coli bacilli.The double pigtail stent and nasal bile duct were installed under EUS (16 patients) or duodenoscope (6 patients).The lesions of 9 patients with pancreatic abscess were healed after endoscopic transgastric debridement with an average period of (6.5 + 1.8 )weeks,and the lesions of 13 patients with pancreatic cyst and infection were healed after transgastric puncture and drainage under the guidance of EUS with an average period of ( 8.3 ± 2.1 ) weeks.All patients were followed up for 2 years,and no recurrence of pancreatic abscess or pancreatic cyst was observed.ConclusionThe effect of transgastric endoscopic surgery for the treatment of pancreatic abscess or pancreatic cyst and infection is satisfactory.
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Objective To evaluate the feasibility of endoscopic resection and closure for non-intraluminal gastric stromal tumors originating from the muscularis propria layer.Methods Included in the study were 46 patients with gastric submucosal lesions originating from the muscularis propria layer, detected by gastroscopy and endoscopic ultrasonography.The lesions were removed by endoscopic resection and closure, which were further diagnosed as stromal tumor by means of pathologic and immunohistochemical examinations.The patients were followed up with endoscopy for evaluation of therapeutic effect and complications.Results All lesions were successfully removed, with serosa layer remained in 2 cases and full layer resection in other 44, which were all closed by endoscopic clips.Combination managements of acid suppression,gastrointestinal decompression and intravenous antibiotics were applied in all patients.Pathology reports confirmed complete resection of all lesions, with 0.5 to 3.7 cm in diameter.Normal diet was restored in 44 patients 48 ～ 72 h after the procedure.Pneumoperitoneum and focal peritonitis occurred in 2 cases, one of which underwent rupture and was clamped again.The 2 patients recovered after 10-12 days of conservative treatments.Follow-up endoscopy revealed white ulcerous scar in all cases.Conclusion Endoscopic resection and closure therapy is a safe, economic and less invasive treatment for non-intraluminal gastric stromal tumors originating from the muscularis propria layer.
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Objective To evaluate the effect of the dimethicone powder in bowel preparation before capsule endoscopy (CE) and to observe its possible adverse effects. Methods A total of 60 patients receiv-ing CE were prospectively randomized into 2 groups according to bowel preparation method. In dimethicone powder group, patients were arranged to take dimethicone powder 30 rain before the examination on basis of macrogol electrolytes powder and in control group, patients had macrogol electrolytes powder only. Images of small intestine were equally divided into segments A, B and C according to intestinal transit time, and re-viewed by 2 experienced physicians independently. Intraluminal gas bubbles were graded and any possible adverse effects were monitored. Results Interobserver agreement was excellent (P < 0.05). In segments A and C, images from dimethicone powder group were less interfered by gas bubble than those from control group (P < 0. 05), but in segment B there was no difference between 2 groups (P > O. 05). No adverse effects were observed. Conclusion The dimethicone powder administration before capsule endoscopy im-proves the visualization of the intestinal mucosa.
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Objective To evaluate the value of electronic video endoscopy for adults in upper gastrointestinal disease in children. Methods Results of video endoscopy for adults performed on 128 children with abdominal pain, upper gastrointestinal hemorrhage, accidental foreign bodies, and esophageal stenosis were analyzed retrospectively. Results The total positive detection rate was 100%. The incidence rates of chronic superficial gastritis and/or duodenitis, peptic ulcer, and foreign bodies were 64.84%, 25.78%, and 8.59%, respectively. Only 1 case of esophageal stenosis was found. Conclusion Video endoscopy for adults, also safe for children, is of significant value in the etiological diagnosis of upper gastrointestinal disease in children.
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Objective To investigate the correlation of oncosis and TNF-? in D-galactosamine (D-GalN) induced acute hepatic injury. Methods Acute hepatic injury model was induced by D-GalN in 24 SD rats, and 12 rats served as control. At 4, 8, 12, 16, 20, 24 h after intraperitoneal injection of D-GalN, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, and the tumor necrosis factor-? (TNF-?) in liver tissue were measured. The pathological changes of liver and the oncosis of hepatocytes were observed by TEM. Results In acute hepatic injury, the levels of ALT, AST, TNF-? mRNA, OI were higher than that of control group (P
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Objective To observe the curative effect and sid e effect of the gastrokinetic agent mosapride citrate by RCT. Methods 42 cases of functional dyspepsia (FD) were divided into two groups rando mly, the group of mosapride(21 cases):orally administrated mosapride, 5mg, t.i.d for 4 weeks, and the control (21 cases):orally administrated domperidone, 5mg, t.i.d for 4 weeks. Symptoms and side effects were recorded before and at d 14, d 28 after administration of the medicines according to GCP and double blind pri ciple. Gastric empting test was also carried out in randomly selected patients. Results Mosapride and domperidone were significantly effective on alleviating symptoms of the patient with FD. In mosapride treated group the half emptying time was shortened and the 120 min remain rate was reduced. No sid e effect was found. Conclusion These results suggest that mosa pride 5 mg t.i.d. is effective and safe on alleviating symptoms of patients with FD and improving the ga stric empting time.