Novel Prognostic Nomograms Based on Inflammation-Related Markers for Patients with Hepatocellular Carcinoma Underwent Hepatectomy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Hepatocellular carcinoma (HCC) is an aggressive disease with high recurrence rate. However, current staging systems were lack of predictive capacity for HCC recurrence. We aimed to develop prognostic nomograms based on inflammation-related markers for HCC patients underwent hepatectomy. MATERIALS AND METHODS: We recruited 889 surgically treated patients from two medical centers. Independent prognostic factors were identified by cox regression analyses. Nomograms for recurrence-free survival (RFS) and overall survival (OS) were established, and validated internally and externally. The performance, discrimination, and calibration of nomograms were assessed, and compared with existed staging systems. RESULTS: Neutrophil to lymphocyte ratio (NLR) and gamma-glutamyl transpeptidase to platelet ratio (GPR) were the two inflammation-related factor that independently correlated with survival. NLR, GPR, international normalized ratio (INR), microvascular invasion, satellite lesions, tumour number, tumour diameter, and macrovascular invasion were used to construct nomogram for RFS while GPR, total bilirubin, INR, α-fetoprotein, microvascular invasion, satellite lesions, tumour diameter, and macrovascular invasion were for OS. In the training cohort, the C-index of nomogram was 0.701 (95% confidence interval [CI], 0.669 to 0.732) for RFS and 0.761 (95% CI, 0.728 to 0.795) for OS. These results received both internal and external validation with C-index of 0.701 (95% CI, 0.647 to 0.755) and 0.707 (95% CI, 0.657 to 0.756) for RFS, and 0.706 (95% CI, 0.640 to 0.772) and 0.708 (95% CI, 0.646 to 0.771) for OS, respectively. The nomograms showed superior accuracy to conventional staging systems (p<0.001). CONCLUSION: The nomograms based on inflammation-related markers are of high efficacy in predicting survival of HCC patients after hepatectomy, which will be valuable in guiding postoperative interventions and follow-ups.

Apatinib increases radiosensitivity of gastric cancer by inhibiting VEGF pathway / 中国病理生理杂志

AIM:To investigate radiosensitization effect of apatinib, a vascular endothelial growth factor (VEGF) receptor2 tyrosine kinase inhibitor, on human gastric carcinoma cell line SGC-7901 and its mechanism.METHODS:SGC-7901 cells were divided into control group, apatinib group, radiotherapy group and combination group.The cell viability was measured by CCK-8 assay.The changes of cell apoptosis and cell cycle were analyzed by flow cytometry.The protein levels of cell apoptosis biomarkers, such as PARP, cleaved caspase-9, cleaved caspase-3 and Bcl-2, and cell proliferation biomarkers, p-PLCγ1 and p-ERK1/2, were detected by Western blot.γ-H2AX expression was detected by immunofluorescence.RESULTS:Compared with apatinib group and radiation group, the cell viability was inhibited after treatment with both apatinib and X-ray (P<0.01).The protein levels of cell proliferation markers p-PLCγ1 and p-ERK1/2 were down-regulated.The cell apoptosis was enhanced (P<0.01).The protein levels of cell apoptosis makers such as PARP, cleaved caspase-9 and cleaved caspase-3 were up-regulated, while Bcl-2 was down-regulated.The disappearance of γ-H2AX foci in the nucleus was delayed, indicating that apatinib impaired the repair of radiation-induced DNA double-strand breaks.The proportion of G2 phase was significantly increased (P<0.01).The combination treatment had more significant effect on SGC-7901 cells than treating with apatinib or radiotherapy alone.CONCLUSION:Apatinib increases the radiosensitivity of gastric cancer cells via blocking VEGF pathway.

Effect of metformin on colorectal carcinoma in type 2 diabetes mellitus patients: a Markov model analysis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the colorectal cancer (CRC) prevention effect of metformin in comparison with that of other T2DM medications from a Markov model perspective.</p><p><b>METHODS</b>Literature concerning CRC morbidity of T2DM patients with metformin or other diabetes medications treatment was reviewed in PubMed and Cochrane Library database from September 2010 to December 2016.</p><p><b>INCLUSION CRITERIA</b>(1)enrolled population was adult patients with T2DM but without CRC; (2) any of the parameters applied in our model was reported; (3) randomized clinical trials (RCTs), quasi-randomized trials, prospective or retrospective cohort studies. With CRC morbidity as endpoint, parameters were extracted to construct Markov model to assess CRC morbidity and cumulative tumor-free survival in each group over 11 years' follow-up period. Finally, Monte Carlo analysis was performed to evaluate the influence of parameter instability on the model.</p><p><b>RESULTS</b>Seven literatures were recruited and 10 000 patients were virtually allocated for each arm. In contrast with non-metformin group, T2DM patients treated with metformin had a lower rate of CRC(1.670% vs. 2.146%, P=0.016). Moreover, cumulative tumor-free survival of metformin group was, slightly but significantly, better than that of non-metformin group (10.908 years vs. 10.882 years, P=0.000).</p><p><b>CONCLUSIONS</b>T2DM patients treated with metformin have a lower morbidity of CRC and a better cumulative tumor-free survival than those of non-metformin group. Large scale RCTs are needed to illustrate the role of metformin in the prevention of CRC.</p>

Characteristics of achalasia:a high-resolution manometry study / 中华消化内镜杂志

Objective To evaluate the clinical and manometric characteristics of achalasia.Meth-ods Patients diagnosed as having achalasia from July 2010 to July 2014 at our hospital were enrolled.High resolution manometry(HRM)results were analyzed.Data of Eckardt scale,MDADI and SF-36 were ana-lyzed.Results All subjects had dysphagia,35.6% (37 /104)accompanied with regurgitation,26.9%(28 /104)with heartburn and 17.3%(18 /104)with weight loss.According to HRM results and Chicago classification criteria,16.35%(17 /104)of the subjects were classified as type Ⅰ,76.92%(80 /104)as type Ⅱ and 6.73%(7 /104)as type Ⅲ.27.9%(29 /104),19.2%(20 /104)and 24.0%(25 /104)of the subjects finished Eckardt scale,MDADI and SF-36,respectively.Eckardt score was positively correlated with integrated relaxation pressure(IRP)(r =0.421,P <0.05)and MDADI physical score was negatively with IRP(r =-0.530,P <0.05).Conclusion Dysphagia often occurs as the chief complaint among acha-lasia patients.And type Ⅱ is the most common.IRP is an indicator of the severity of clinical symptoms and impairment of quality of life.

Changes of esophageal intraluminal baseline impedance in 47 reflux esophagitis / 中华消化杂志

Objective To investigate the changes of esophageal intraluminal baseline impedance in patients with refluxesophagitis.Methods From December 2013 to August 2014,47 patients with reflux esophagitis and 17 healthy controls were enrolled.The patients with reflux esophagitis were graded according to Los Angeles classification (LA) grading standards.All subjects accepted 24 h multichannel intraluminal impedance (MII) pH examination,and the baseline value of impedance were measured.Independent sample t test was used to compare the difference in impedance between the two groups.Spearman rank correlation coefficient was performed to analyze the correlation between acid exposure time (AET) and the baseline impedance of patients with reflux esophagitis.Kruskal-Wallis test was used to compare the differences in baseline impedance of patients with different grades of reflux esophagitis.Results The impedance baseline value of reflux esophagitis group was (1 676.72±644.41) Ω,which was lower than that of healthy control group ((2 151.27± 322.05) Ω),and the difference was statistically significant (t =-3.883,P＜0.01).The AET of esophagus was negatively correlated with the baseline impedance of the patients with reflux esophagitis (r=-0.530,P＜0.01).The baseline impedance of patients with grade LA-A and grade LA-B reflux esophagitis were 1 823.62 Ω (1 515.38 52 Ω,2 208.38 Ω) and 1 771.81 Ω(1 304.75 52 Ω,2 080.50 Ω),respectively,and the difference was not statistically significant (Z=-0.630,P=0.529).The baseline impedance of patients with grade LA C/D reflux esophagitis was 300 Ω (300 Ω,500 Ω),which was obviously lower than those of patients with grade LA-A or grade LA-B (Z=-2.647 and-2.818,both P＜0.017).Conclusion The baseline impedance of patients with reflux esophagitis is low and correlated with AET.

Relationship between symptom response and esophageal pH level on standard dose of esomeprazole treatment for gastroesophageal reflux disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The relationship between symptom elimination and normalization of esophageal acid level of gastroesophageal reflux disease (GERD) on proton-pump inhibitor (PPI) therapy has been questioned. This study aimed to evaluate the relationship between symptom response and gastro-esophageal acidity control in Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24-hour esophageal pH-metry after therapy in GERD patients.</p><p><b>METHODS</b>GERD patients with typical reflux symptoms were enrolled and received esomeprazole 40 mg once daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry were divided into two groups depending on an additional dual-channel 24-hour pH-metry after treatment. The pH- group achieved normalization of esophageal pH level whereas the pH+ group did not.</p><p><b>RESULTS</b>Of the 80 patients studied, 76 had abnormal baseline esophageal pH levels. Of these, 90% (52/58) of symptom-free patients and 67% (12/18) of symptom-persistent patients achieved esophageal pH normalization after therapy (P = 0.030). The mean post-therapy gastric nocturnal percent time of pH < 4.0 was significantly higher in pH+ group than that in pH- group (P < 0.001) after therapy. The multivariate regression analysis identified hiatus hernia (P < 0.001) and persistent reflux symptom (P = 0.004) were two independent factors predicting the low post-therapy esophageal pH level.</p><p><b>CONCLUSIONS</b>Symptom elimination is not always accompanied by esophageal pH normalization, and vice verse. Esophageal pH-metry is recommended for GERD patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.</p>

A population-based epidemiologic study of bowel habits in Guangdong province / 中华流行病学杂志

Objective To determine the bowel habits and its perceptions in the general population of Guangdong province. Methods Random clustered sampling involving permanent inhabitants aged 18-80 year was carried out under stratification of urban and suburban areas in Guangdong province. Questionnaire included the items on the characteristics of people being selected and their bowel habits. Results A total of 4103 residents (male 1878, female 2225) were investigated. Mean age among the responders was 42.81 ± 14.13 year. Among 4056 subjects (missing =47 ), 2972 subjects (73.3%) reported daily defecation, and 3951 subjects (97.4%) reported stool frequency between 3 times per week and three times per day. Two hundred and seventy subjects (6.6%) reported abnormal bowel habits by themselves. The stool frequency (OR=2.03, 95% CI:1.54-2.67) , forms of stool (OR=2.75, 95% CI: 2.35-3.22) and straining (OR=3.56, 95% CI:2.49-5.11) were significantly associated with self-reported abnormal bowel habits. Among 3949 subjects (missing= 154), 644 (16.3%) were defined as having abnormal bowel habits according to Rome Ⅱ criteria. There was poor agreement between self-reported abnormal bowel habits and that defined by Rome Ⅱ criteria (Kappa=0.312). Conclusion It seemed to be appropriate that the normal stool frequency was defined as bowel movements between 3 times per week and three times per day in the general population. The prevalence of self-reported abnormal bowel habits was lower than that defined by Rome Ⅱ criteria and the agreement between these two definitions was poor.

Correlates of health-care seeking behavior in patients with irritable bowel syndrome / 中华全科医师杂志

Objective To explore correlates of health-care seeking behavior in patients with irritable bowel syndrome (IBS).Methods Four thousand permanent residents were recruited from eight urban communities and rural villages in Guangzhou and Huizhou, Guangdong province during 2009 by cluster stratified sampling for face-to-face questionnaire survey, including symptoms of bowel disease,behavior of seeking for health-care, demographic characteristics, coping style, life events and medical history.IBS was identified based on the Rome Ⅱ Criteria.Patient with IBS were divided into two groups,one seeking health-care at hospitals or clinics and the other non-seeking health-care.Univariate and multivariate logistic regression analysis was used to compare difference between the two groups and explore its related factors.Results A total of 237 IBS patients were identified based on the Rome Ⅱ Criteria, 53 of them (22.4% ) had sought health-care due to their symptoms.Results of multivariate logistic regression analysis showed that preference in seeking for health-care, abdominal pain lasting for more than one hour in each episode and extra-gastrointestinal symptoms were main factors related to their seeking for health-care,adjusted for age and gender, with odds ratios (ORs) of 1.81 (95% CI: 1.27 -2.58), 1.41 (95% CI:1.01 - 5.14 ) and 2.14 ( 95% CI: 1.06 - 4.33 ), respectively.Conclusions Extra-gastrointestinal symptoms and abdominal pain lasting for more than one hour in each episode correlate their health-care seeking behavior in patients with IBS, as well as their preferences in seeking for health-care.

The value of gastrointestinal endoscopy in diagnosis of patients with typical heartburn / 中华消化杂志

Objective To evaluate the value of endoscopic profile in an adult population with typical heartburn. Methods Clinical and endoscopic data were collected from 5042 consecutive outpatients who underwent routine upper endoscopy without any alarm features between March 2006 and Feb. 2007. Results Three hundred and thirteen (6.2%) patients were diagnosed as having typical heartburn. Of these, erosive esophagitis (EE) was found in 99 (31.6%) patients, Barrett's esophagus (BE) in 10 (3. 2%) patients, peptic ulcer disease (PUD) in 21 (6. 7%) patients and carcinoma in three (0.9 %) patients (1 with esophageal carcinoma and 2 with gastric adenocarcinoma).Multivariate analysis revealed that age＞50, male, overweight and alcohol use were independent risk factors for positive endoscopy findings (P＜0.05) and EE (P＜0.05) in heartburn patients. Male and Helicobacter pylori infection were independent risk factors for PUD (P＜ 0.05). Conclusions In China, patients with typical heartburn but without alarm features, early endoscopic examination may be helpful in avoiding missing diagnosis of tumor.

Value of combined multichannel intralumminal impedance-pH monitoring in the diagnosis of gastroesophageal reflux disease / 中华消化杂志

Objective To investigate the role of combined multichannel intralumminal impedanee-pH (MII-pH) monitoring in the diagnosis of gastroesophageal reflux disease (GERD). Methods Forty-four consecutive patients, who had heartburn symptom and without esophageal mucosal lesion, underwent combined MII-pH monitoring. Then rabeprazole test was performed for 14 days with 10 mg twice daily. Rabeprazole test was defined as positive if patients were totally heartburn symptom free in the second week. The normal values from 70 healthy volunteers who underwent MII-pH monitoring were served as controls. Results Conventional esophageal pH monitoring showed that 20 patients (45.5%) had pathologic esophageal acid exposure or positive acid reflux associated symptom index. MII-pH monitoring revealed that 2 patients were positive for weakly acidic reflux related to symptom index, thus increased the diagnostic yield to 50% (22/44). Furthermore, rabeprazole test demonstrated that 4 patients were positive which increased the diagnostic yield to 54.5%(24/44). Conclusion The detective rate of GERD will be elevated if combined with MII-pH monitoring in diagnosis.

The value of esomeprazole test in diagnosing gastroesophageal reflux disease:A randomized multi-center controlled trial / 中华消化杂志

Objective To evaluate the diagnostic value of esomeprazole test in patients with gastroesophageal reflux disease.Methods Consecutive patients with heartburn and/or acid regurgitation in three medical centers were enrolled in a prospective,randomized,double-blind study with a placebo-control design.After upper endoscopy examination,patients were divided into non-erosive reflux diseases and erosive esophagitis.All patients underwent 24-hour ambulatory esophageal pH monitoring.Those who were diagnosed as gastroesophageal reflux diseases had either esophagitis under endoscopy or abnormal esophageal acid exposure in 24-hour ambulatory esophageal pH monitoring.The patients were randomly divided into treatment group and control group.The patients in treatment group were received 40 mg of esomeprazole daily while the patients in control group were given placebo once daily for 14 days.The severity and frequency of heartburn were recorded both by doctors and patients before and during treatment.Results Two hundred and seventeen patients were completed the study(105 patients in treatment group and 112 patients in control group).If the symptom of heartburn which disappeared in the sixth and seventh day of the first week,it was defined as positive for esomeprazole test,the sensitivity and specificity in treatment group were 87.7% and 42.5%,respectively If the symptom of heartburn disap peared in the second week,it was defined as positive for esomeprazole test.The corresponding sensitivity and specificity in treatment group were 84.6% and 45%,respectively.The Youden index was 0.362 and 0.296 for criteria of one and two weeks,respectively.If the heartburn score improved by more than 50%,75% or 100% from the baseline score after treatment,it was defined as positive for esomeprazole test,the sensitivity and specificity were 95.4% and 32.5%,87.7% and 32.5%,84.6% and 45%,respectively.Conclusions The esomeprazole test has high value in diagnosis of GERD with sensitivity of 87.7% and specificity of 42.5%.Positive definition of heartburn disappeared in the sixth and seventh day is superior in cost-effective.

Impact of risk factors on the severity of esophageal mucosal injury in patients with gastroesophageal reflux disease / 中华消化内镜杂志

Objective To assess the risk factors that could influence the severity of esophageal inju- ry in patients with gastroesophageal reflux disease(GERD).Methods GERD patients diagnosed on the ba- sis of endoscopic reflux esophagitis or pathological results of 24 hour esophageal pH monitoring were divided into three groups as non-erosive reflux disease group(NERD)(n=83),mild esophagitis group(n=51) and severe esophagitis group(n=22).The clinic data and esophageal pH parameters were recorded in the three groups.A logistic regression was used to assess the joint influences of clinic characteristics,hiatus her- nia,and esophageal pH parameters on the severity of esophageal injury.Results Patients in severe esoph- agitis group were more likely to have advanced age and hiatus hernia.The number of supine long reflux epi- sodes measured by esophageal pH monitoring significantly increased with increasing grades of mueosal dam- age(P