Construction of CTC-ALK gene fusion detection system based on the multi-site magnetic separation in lung cancer and its clinical verification.

Detected in a variety of solid tumors, including lung cancer, the EML4-ALK fusion gene plays an important role in promoting the occurrence and development of cancer. The existing detection methods for EML4-ALK fusion gene are all targeted at surgical or post-sampling tumor tissues, which cannot achieve early detection and real-time monitoring; therefore, a minimally invasive ALK gene fusion detection system is explored and constructed. Vimentin, EpCAM, and EGFR antibodies were grafted, respectively, to prepare multi-site immunoliposome magnetic beads, so as to capture CTC in blood for RT-PCR detection, and then the feasibility of this method was verified by detecting the positive rate of the EML4-ALK fusion gene and clinical information in combination with WB and IHC. The prepared multi-site immunoliposome magnetic beads showed high specificity and stability, and the average proliferation rate and capture rate of cells were 95% and 85%, respectively. In clinical blood samples, the CTC level of the grade I (G1) patients before the operation was lower than grade 2 (G2), and that of grade II (G2) was significantly lower than grade III (G3), but the difference was not significant after the operation. The RT-PCR results of CTC and the RT-PCR, WB, and IHC results of tissues were highly consistent in the fusion gene detection, and the positive rate of ALK gene fusion in 60 lung cancer patients was 31.67% and 28.33% before and after the operation, mostly EML4-ALK (V3) gene fusion. The CTC-ALK gene fusion detection system constructed successfully could avoid the problem of difficult sampling and post-sampling complications, and truly achieve the minimally invasive biopsy, so it was of important clinical significance for the diagnosis and efficacy evaluation of lung.

[Covered airway stent loaded with (125)I seeds for tracheal adenoid cystic carcinoma: a clinical observation of 8 cases].

Objective: To explore the efficacy and safety of the covered airway stent loaded with (125)I seeds for the treatment of tracheal adenoid cystic carcinoma (TACC). Methods: We retrospectively reviewed the clinical data from 8 patients with TACC who had received placement of the covered stent loaded with (125)I seeds between December 2014 and July 2017 in the endoscopic center of the Second Affiliated Hospital of Xiamen Medical College. We compared the difference in the dyspnea index, the diameter of the airway lumen, and the lesion surrounding the airway wall before and after treatment. The complications were also recorded during follow-up. Results: Eight patients underwent successful placement of a total of 11 radioactive stents (2 straight-type stents, 2 L-shape stents, and 7 Y-shape stents, all loaded a total of 243 radioactive particles). Displacement of stents took place within 2 weeks in 2 patients, who were managed with re-stenting and fixation. No further displacement occurred during follow-up. The median time to stent removal was 2.9(interquartile range: 2.3,3.0) months. After stent placement, the dyspnea index was significantly decreased compared with pre-treatment level (mean: 0.1 vs. 3.4, t=8.881, P<0.001). Bronchoscopic re-assessment showed that the residual tumor within the airway was detected in only one patient and that the tumor completely disappeared in the remaining 7 patients. Treatment with stents loaded with radioactive particles yielded smooth and pale airway mucosa with formation of partial scar formation. Chest computed tomography re-assessment demonstrated significantly larger luminal diameter than that before treatment (mean: 13.1 mm vs. 3.3 mm, t=-7.839, P<0.001). The airway wall thickness was notably reduced after treatment (mean: 4.3 mm vs. 14.4 mm, t=7.620, P<0.001). The lesions surrounding the airway wall completely disappeared in 7 patients and decreased for more than 50% in a single patient. The median duration of follow-up was 28.0(interquartile range: 24.8,31.5) months. Recurrence of tumor was documented in a single case within 2 years. Six patients did not experience recurrence within the 2-year follow-up period. No death or severe complications were recorded during follow-up. Conclusion: The (125)I radioactive stent is effective for dilating the stenotic airway and ameliorating the symptoms, and thus might be an effective and safe method for the treatment of TACC. Further studies that explore the efficacy of stents loaded with (125)I particles are needed.

The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference.

BACKGROUND: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined. AIM: To determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders. METHODS: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor. RESULTS: Data from 2884 patients were included. Minimal important difference estimates ranged from -0.52 to -0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates. CONCLUSIONS: Anchor-based methods gave consistent results for the minimal important difference, at approximately -0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg -0.75) could be used in clinical trials to reduce the placebo response rate.

The motility of esophageal sphincters during liquid and solid bolus swallows: a multicenter normative value study of high-resolution manometry in China.

BACKGROUND: It is gradually accepted that solid bolus swallow needs to be added to the procedure of manometry. The motility differences in the upper esophageal sphincter (UES) and lower esophageal sphincter (LES) were not well described. Sierra Scientific Instruments solid-state high-resolution manometry (HRM) system, the most popular HRM system in China, lacks the Chinese normative values for both liquid and solid bolus swallow parameters. METHODS: The esophageal HRM data of 88 healthy volunteers were analyzed. The parameters of both sphincters in resting stage were summarized and those during solid and liquid swallows were compared. KEY RESULTS: Normative HRM values of sphincter parameters in solid and liquid bolus swallows in China were established. The UES residual pressure of solid bolus swallows was lower than that of liquid bolus (0.3±5.5 mm Hg vs 4.8±5.9 mm Hg, P=.000). The time parameters of UES relaxation between two types of bolus swallows were similar. In solid bolus swallows, the intrabolus pressure (IBP) (13.8±5.1 mm Hg vs 10.9±5.7 mm Hg, P=.000) and LES relaxation time (11.0±2.1 seconds vs 8.7±1.3 seconds, P=.000) were higher. The 4-second integrated relaxation pressure between both bolus swallows was similar. CONCLUSIONS & INFERENCES: The function of the UES and LES between solid and liquid bolus swallows is different. Chinese HRM parameters are different from the Chicago Classification (http://www.chictr.org.cn, Number ChiCTR-EOC-15007147).

The FIB-4 score predicts postoperative short-term outcomes of hepatocellular carcinoma fulfilling the milan criteria.

BACKGROUND: The fibrosis score 4 (FIB-4) score is a useful tool to determine the degree of hepatic fibrosis. Liver fibrosis and cirrhosis are well-known predictors of postoperative complications after hepatectomy. This study examined the impact of FIB-4 on postoperative short-term outcomes of patients with hepatocellular carcinoma (HCC). METHODS: Three hundred and fifty patients undergoing hepatectomy for HCC between 2008 and 2013 were enrolled. The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the FIB-4. Univariate and multivariate analysis was performed to identify the risk factors. The correlation of the preoperative FIB-4 value with clinicopathological parameters was examined. RESULTS: Postoperative complications were observed in 202 (57.7%) patients. The optimal cutoff value of the FIB-4 was set at 2.88 and 3.85 for postoperative complications and intraoperative blood loss respectively. It was also an independent prognostic factor for postoperative complications (hazard ratio [HR], 1.202; 95% CI, 1.076-1.344; P = 0.001) and intraoperative blood loss (HR, 1.196; 95% CI, 1.091-1.343; P < 0.001) by multivariate analysis. The FIB-4 was significantly correlated with age, liver function, coagulation function, blood loss, intraoperative blood transfusion (all P < 0.05). CONCLUSION: Preoperative FIB-4 is a useful index to predict postoperative outcomes in patients with HCC. The FIB-4 should be assessed routinely for hepatocellular carcinoma patients.

Cisapride provides symptomatic relief in functional dyspepsia associated with gastric myoelectrical abnormality.

OBJECTIVE: We evaluated the effects of cisapride (10 mg t.d.s. and 20 mg b.d.) on gastrointestinal symptoms and gastric myoelectrical activity in patients with functional dyspepsia. Myoelectrical activity was measured by electrogastrography. METHODS: Patients with functional dyspepsia, defined as discomfort in the epigastrium, a negative endoscopy, and clinical symptoms of dyspepsia, were enrolled. A total of 38 patients participated in the study (23 female; 15 male; 24-72 years of age). Screening electrogastrography identified those with a normal electrogastrogram (14 subjects) and those with an abnormal electrogastrogram (24 patients). Patients were randomly assigned to 2 weeks of placebo or 2 weeks of cisapride (10 mg t.d.s.); both groups then received 2 weeks of cisapride (20 mg b.d.). Electrogastrograms were repeated at the end of each 2-week treatment period. RESULTS: Cisapride 10 mg t.d.s. significantly improved symptoms in all patients. An additional 2 weeks of treatment with cisapride 20 mg b.d. led to continued improvement in symptoms in all patients, with significant improvement in the group with abnormal baseline electrogastrograms. Cisapride significantly improved postprandial bloating and discomfort in patients with abnormal baseline electrogastrograms. Cisapride also significantly improved postprandial gastric myoelectrical activity as measured by electrogastrography in patients with abnormal baseline electrogastrograms. CONCLUSION: Cisapride provides symptomatic relief and improves gastric myoelectrical abnormalities in patients with functional dyspepsia.

[Diagnosis and treatment of angina-like chest pain in 52 cases].

Esophageal investigation was performed successfully in 52 patients who were initially suspected of suffering from angina pectoris, but the pain was subsequently shown to be not of cardiac origin by radionuclide myocardiac perfusion and (or) coronary angiography in 74% of cases, and by EKG and poor response to anti-angina therapy in 26% of the cases. In 82.7% of the patients the diagnosis was gastroesophageal reflux disease (GERD), in 3.8% Nutcracker esophagus, and in 5.8% lower esophageal sphinctor hypertension. In the remaining 7.7% the diagnosis was unknown. In 43 patients with GERD, gastroesophageal reflux (GER) investigation showed GER symptoms in 61.5%, reflux esophagitis was confirmed with endoscopy in 45.3%. Abnormal esophageal manometry was found in 53.8%, positive provocative test in 42.9%, excessive radionuclide GER in 50%, and increased duration of hyperacidity in 57.1%. However, a combined study of the procedures mentioned above showed that the diagnosis was consistent with GERD in 82.3% of the patients. Chest pain was completely relieved in 34% of the cases and significantly relieved in 50%. No response was ilicited in 16% of the cases after 1-2 weeks of anti-reflux therapy. It is found that chest pain induced by GERD is very common, esophageal endoscopy and motor studies are helpful in the diagnosis of GERD and other esophageal motor diseases, and anti-reflux therapy is a reliable measure when a patient complains of unknown chest pain and GER symptoms.

[Gastrointestinal transit time (GITT) in normal Chinese and patients].

Two kinds of radiopaque pellets were ingested as markers to determine GITT in 60 normal subjects, 7 patients with ulcerative colitis (UC), 10 patients with idiopathic constipation (IC) and 8 patients with other diseases. The food contained 10-20g dietary fiber per day. Besides, GITT was determined in 14 normal subjects whose dietary content was 40-50g or 10g MO YU and 10-20g dietary fiber per day. Results are expressed in hours as 50% transit time (mean +/- s) and the values or normal subjects are as the follows: total GITT 25.0 +/- 7.3h, mouth iteum TT 9.0 +/- 3.3h, colonic TT 15.9 +/- 7.5h. There was no difference in age or sex groups. However, in high dietary fiber or MO YU group, GITT shortened significantly. Abnormal GITT was shown in patients with UC, IC, other gut and systemic diseases. In conclusion, the method employed in the present study is simple, safe and useful in the clinical study of gastrointestinal motility; and may provide important information to elucidate the pathophysiology of the diseases related to disorders in motility of the digestive tract.

[Omeprazole in peptic ulceration: acid inhibition and endoscopic healing].

Basal and pentagastrin stimulated gastric acid secretions were measured in 20 patients with duodenal ulcer before and after one week of treatment with oral omeprazole 20 mg daily. Omeprazole markedly inhibited gastric acid secretion in all the patients. The mean basal intragastric pH rose from 1.6 to 6.3, and the BAO and MAO were reduced by 86.9% and 83.9% respectively on day 7 of the study. We also conducted a clinical trial in 63 duodenal and 12 gastric ulcer patients. Each patient received 20 mg omeprazole. 98% of the patients were free of pain within first week of the treatment. After 2, 4 and 6 weeks of treatment, the healing rates of duodenal ulcer were 81.3%, 96.8% and 100% respectively, and those of gastric ulcer were 50%, 91.7% and 100% respectively. The drug was well tolerated and no side effect was observed.