Double-tract reconstruction is superior to esophagogastrostomy in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy:Results from a prospective randomized controlled clinical trial in China

Objective:The aim of this study was to prospectively compare double-tract reconstruction(DTR)and esophagogastrostomy(EG)after proximal gastrectomy(PG)regarding the incidence of reflux esophagitis,quality of life(QOL),nutritional status and surgical safety.Methods:This study was a randomized controlled trial.Patients eligible for PG were enrolled and randomly assigned to the EG group and DTR group.The characteristics of patients,parameters for surgical safety,incidence of reflux esophagitis,nutrition status and QOL were collected and compared between the two groups.Univariate analysis and multivariate analysis were performed to determine the significant factors affecting the incidence of reflux esophagitis after PG.Results:Thirty-seven patients of the EG group and 36 patients of the DTR group were enrolled.The incidence of reflux esophagitis was significantly lower in the DTR group than in the EG group(8.3%vs.32.4%,P=0.019).The DTR group demonstrated a more favorable QOL than the EG group after PG.The nutritional status was balanced within the EG group and the DTR group.The operation time was longer in the DTR group than in the EG group(191 min vs.221 min,P=0.001),while surgical safety was similar in the two groups.Conclusions:Our research demonstrated that DTR is superior to EG after PG in terms of the incidence of reflux esophagitis and provides a more satisfactory QOL without increasing surgical complications or sacrificing nutritional status.

LGR5 is a promising biomarker for patients with stage Ⅰ and Ⅱ gastric cancer

Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. Results： The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues （P〈0.001）, and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II （P〈0.05）. Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn＇t meet statistical significance （P〉0.05）. LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients （P〈0.05）. Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival （P〈0.05）. Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer （P〈0.05）. Conclusions： Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.

Depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis

Objective： Diagnostic laparoscopy is recommended for the pretherapeutic staging of gastric cancer to detect any unexpected or unconfirmed intra-abdominal metastasis. The aim of this study was to evaluate the role and indications of diagnostic laparoscopy in the detection of intra-abdominal metastasis. Methods： Standard diagnostic laparoscopy with peritoneal cytology examination was performed prospectively on patients who were clinically diagnosed with primary local advanced gastric cancer （CT≥2M0）. We calculated the rate of intra-abdominal metastases identified by diagnostic laparoscopy, and examined the relationship between peritoneal dissemination （P） and cytology results （CY）. Split-sample method was applied to find clinical risk factors for intra-abdominal metastasis. Multivariate logistic regression analysis and receiver-operator characteristic （ROC） analysis were performed in training set to find out risk factors ofintra-abdominal metastasis, and then validate it in testing set. Results： Out of 249 cM0 patients, 51 （20.5%） patients with intra-abdominal metastasis were identified by diagnostic laparoscopy, including 20 （8.0%） P1CY1, 17 （6.8%） POCY1 and 14 （5.6%） P1CY0 patients. In the training set, multivariate logistic regression analysis and ROC analysis showed that the depth of tumor invasion on computer tomography （CT） scan ≥21 mm and tumor-occupied 〉2 portions of stomach are predictive factors of metastasis. In the testing set, when diagnostic laparoscopy was performed on patients who had one or two of these risk factors, the sensitivity and positive predictive value for detecting intra-abdominal metastasis were 90.0% and 32.1%, respectively. Conclusions： According to our results, depth of tumor invasion and tumor-occupied portions of stomach are predictive factors ofintra-abdominal metastasis.

Construction and external validation of a nomogram that predicts lymph node metastasis in early gastric cancer patients using preoperative parameters

Objective: To create a nomogram to predict the incidence of lymph node metastasis(LNM) in early gastric cancer(EGC) patients and to externally validate the nomogram.Methods: To construct the nomogram,we retrospectively analyzed a primary cohort of 272 EGC patients.Univariate analysis and a binary logistic regression were performed.A nomogram predicting the incidence of LNM in EGC patients was created.The discrimination ability of the nomogram was measured using the concordance index(c-index),and the nomogram was also calibrated.Then,another prospective cohort of 81 patients was analyzed to validate the nomogram.Results: In the primary cohort,LNM was pathologically confirmed in 37(13.6%) patients.In multivariate analysis,the presence of an ulcer,the maximum lesion diameter observed via gastroscopy,the thickness of the lesion observed via endoscopic ultrasonography,and the presence of enlarged lymph nodes on computed tomography(CT) were independent risk factors for LNM.A nomogram was then created based on the regression model with the c-index of 0.905,and the calibration curve of the nomogram fell approximately on the ideal 45-degree line.The cut-off score of the nomogram was 110,and the sensitivity,specificity,positive predictive and negative predictive values of the nomogram in the primary cohort were 81.1%,86.0%,47.6% and 96.7%,respectively,and in the prospective validation cohort were 75.0%,91.0%,60.0% and 95.5%,respectively.The calibration curve of the external validation cohort was almost on the 45-degree line.Conclusions: We developed an effective nomogram predicting the incidence of LNM for EGC patients.

Diagnostic value of negative enrichment and immune fluorescence in situ hybridization for intraperitoneal free cancer cells of gastric cancer

Objective:To explore the intraperitoneal free cancer cell(IFCC)detection value of negative enrichment and immune fluorescence in situ hybridization(NEimFISH)on chromosomes(CEN)8/17.Methods:To verify the reliability of NEimFISH,29 gastric cancer tumors,their adjacent tissues and greater omental tissues were tested.Our study then included 105 gastric cancer patients for IFCC.We defined patients as IFCC-positive if a signal was detected,regardless of the detailed cancer cell numbers.A comparison of clinicopathological features was conducted among IFCC groups.We also compared the diagnosis value and peritoneal recurrence predictive value among different detection methods.The comparison of IFCC number was also conducted among different groups.Results:A cutoff of 2.5 positive cells could distinguish all benign tissue samples and 97%of malignant tissue samples in our study.Compared to intestinal gastric cancer,patients with diffuse gastric cancer tended to have more IFCCs(6 vs.4,P=0.002).The IFCC counts were often higher in the lymphovascular invasion positive group than negative group(3 vs.1,P=0.022).All IFCC samples that were considered positive using conventional cytology were also found to be positive using NEimFISH.When compared to conventional cytology and paraffin pathology,NEimFISH had a higher IFCC positive rate(68.9%)and higher one-year peritoneal recurrence predictive value with area under the curve(AUC)of 0.922.Conclusions:Gastric cancer could be effectively diagnosed by NEimFISH.The IFCC number found using NEimFISH on CEN8/17 is closely associated with Lauren type and vascular invasion of cancer.NEimFISH is a reliable detection modality with a higher positive detection rate,higher one-year peritoneal recurrence predictive value and quantitative features for IFCC of gastric cancer.

Postoperative chemotherapy with S-1 plus oxaliplatin versus S-1alone in locally advanced gastric cancer(RESCUE-GC study): a protocol for a phase Ⅲ randomized controlled trial

Background： The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one of the treatment options for gastric cancer patients after radical gastrectomy with D2 lymph node excision. Methods： We have commenced a randomized phase III trial in December 2016 to evaluate S-I plus oxaliplatin compared with S-1 alone in the adjuvant setting for locally advanced gastric cancer. A total of 564 patients will be accrued from 13 Chinese institutions in two years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are 5-year overall survival, proportion of patients who complete the postoperative chemotherapy and incidence of adverse events. Ethic and dissemination： The trial has been approved by the institutional review board of each participating institution and it was activated on December, 2016. The enrollment will be finished in December, 2018. Patient＇s follow-up will be ended until December, 2023. Trial registration： ClinicalTrials.gov, identifier： NCT02867839. Registered on August 4, 2016.

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma

Objective： To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma （MGC） and signet-ring cell carcinoma （SRCC）. Methods： Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using Z2 test. Survival was analyzed using the Kaplan- Meier method and multivariate analysis of Cox proportional hazards regression model （backward, stepwise）. Results： A total of 181 patients with gastric cancer （74 MGC, 107 SRCC） were included. MGC, when compared with SRCC, was featured by senile patients, stage III and I~, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion （P〈0.05）. The overall 5-year survival rate showed no difference between the two groups （48.8% vs. 44.8%, P〉0.05）. However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age 〈60 years, negative distant metastasis, and tumor localized at upper third stomach （P〈0.05）. Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. Conclusions： While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.

Identification of lymph node metastasis by computed tomography in early gastric cancer

Objective:Lymph node status is critical when selecting treatment methods for patients with early gastric cancer(EGC).The aim of this study was to assess the diagnostic value of computed tomography(CT)for detection of lymph node metastasis(LNM)in patients with EGC.Methods:We retrospectively analyzed patients who had pathologically confirmed EGC between November2010 and January 2019.After 1:1 propensity score matching,65 patients with LNM and 65 patients without LNM were retained for comparison.The long diameter(LD)and short diameter(SD)of all visualized lymph nodes in all stations were recorded.The diagnostic value of LNM was assessed with receiver operating characteristic analysis.Results:Among 130 patients,we found a total of 558 lymph nodes on the CT images.Among the diagnostic indicators,the number,sum of LD and sum of SD of lymph nodes greater than 3 mm had better discrimination.The areas under the curve were all greater than 0.75.As for different regions,the optimal cutoff values of number,the sum of LD and sum of SD were determined as follows:overall,≥4,19.9 mm and 13.5 mm;left gastric artery basin,≥3,15.7 mm and 8.6 mm;right gastroepiploic artery basin,≥2,8.6 mm and 7.0 mm.Conclusions:CT is valuable for diagnosing LNM in EGC patients.The number,sum of LD and sum of SD of lymph nodes greater than 3 mm are preferable indicators.Different regional lymph nodes have different optimal criteria for predicting LNM in ECG patients.

Nomogram for predicting lymph node metastasis rate of submucosal gastric cancer by analyzing clinicopathological characteristics associated with lymph node metastasis

Background： To combine dinicopathological characteristics associated with lymph node metastasis for submucosal gastric cancer into a nomogram. Methods： We retrospectively analyzed 262 patients with submucosal gastric cancer who underwent D2 gastrectomy between 1996 and 2012. The relationship between lymph node metastasis and clinicopathological features was statistically analyzed. With multivariate logistic regression analysis, we made a nomogram to predict the possibility of lymph node metastasis. Receiver operating characteristic （ROC） analysis was also performed to assess the predictive value of the model. Discrimination and calibration were performed using internal validation. Results： A total number of 48 （18.3%） patients with submucosal gastric cancer have pathologically lymph node metastasis. For submucosal gastric carcinoma, lymph node metastasis was associated with age, tumor location, macroscopic type, size, differentiation, histology, the existence of ulcer and lymphovascular invasion in univariate analysis （all P〈0.05）. The multivariate logistic old, macroscopic type III or mixed, undifferentiated type, regression analysis identified that age _〈50 years and presence of lymphovascular invasion were independent risk factors of lymph node metastasis in submucosal gastric cancer （all P〈0.05）. We constructed a predicting nomogram with all these factors for lymph node metastasis in submucosal gastric cancer with good discrimination [area under the curve （AUC） =0.844]. Internal validation demonstrated a good discrimination power that the actual probability corresponds closely with the predicted probability. Conclusions： We developed a nomogram to predict the rate of lymph node metastasis for submucosal gastric cancer. With good discrimination and internal validation, the nomogram improved individualized predictions for assisting clinicians to make appropriated treatment decision for submucosal gastric cancer patients.

Characteristics of lymph node stations/basins metastasis and construction and validation of a preoperative combination prediction model that accurately excludes lymph node metastasis in early gastric cancer

Objective:To explore the candidate indications for function-preserving curative gastrectomy and sentinel lymph node navigation surgery in early gastric cancer(EGC).Methods:The clinicopathological data of 561 patients with EGC who underwent radical gastrectomy for gastric cancer at Peking University Cancer Hospital from November 2010 to November 2020 with postoperative pathological stage pT1 and complete examination data,were collected.Pearson’s Chi-square test was used and binary logistic regression was employed for univariate and multivariate analyses.Combined analysis of multiple risk and protective factors for lymph node metastasis(LNM)of EGC was performed.A negative predictive value(NPV)combination model was built and validated.Results:LNM occurred in 85 of 561 patients with EGC,and the LNM rate was 15.15%.NPV for LNM reached 100%based on three characteristics,including ulcer-free,moderately well differentiation and patient<65years old or tumor located at the proximal 1/3 of the stomach.Regarding lymphatic basin metastasis,multivariate analysis showed that the metastatic proportion of the left gastric artery lymphatic basin was significantly higher in male patients compared with female patients(65.96%vs.38.89%,P<0.05).The proportion of right gastroepiploic artery lymphatic basin metastasis in patients with a maximum tumor diameter>2 cm was significantly greater than that noted in patients with a maximum tumor diameter≤2 cm(60.78%vs.28.13%,P<0.05).Conclusions:Characteristics of lymph node stations/basins metastasis will facilitate precise lymph node resection.The NPV for LNM reaches 100%based on the following two conditions:young and middle-aged EGC patients,well-differentiated tumors,and without ulcers;or well-differentiated tumors,without ulcers,and tumors located in the proximal stomach.These findings can be used as the recommended indications for functionpreserving curative gastrectomy and sentinel lymph node navigation surgery.

Uncovering chromatin accessibility and cancer diagnostic potential via cell-free DNA utilization

Gene expression patterns of tumor cells can be inferred from features of circulating cell-free DNA(cfDNA),such as histone modifications and fragmentation patterns at promoters.However,the direct relationship between cfDNA patterns and tumor-specific chromatin accessibility has not yet been experimentally established,limiting its current application to cancer diagnosis alone.

Study on the interaction between inherent minerals of coal with refuse derived fuel(RDF)during co-firing

In this paper,refuse derived fuel(RDF)and bituminous coal were co-fired to investigate the particulate matter(PM)yields and the interaction between the inherit minerals in a lab-scale drop tube furnace(DTF).The PM1-10 yields during the co-firing of coal and RDF dramatically decreased by 16.29%~28.5%of the combustion of coal alone.In addition,methane auxiliary combustion inhibited the PM_(1) yields by 7.95%at air atmosphere.The Si-rich minerals in coal interreacted with the organic alkali(earth)metals in RDF,massively generating sticky particles with high liquid amount of K-Al-Si and Ca-Al-Si,promoting the transformation of fine grains into coarser mode.Moreover,it was proved that both methane auxiliary combustion and co-firing can reduce the emission of fine particles.The additional heat accelerated the burn of the char at the early stage of combustion,providing adequate time for the interaction between the inorganic species.Through thermodynamic equilibrium calculations of 1500~3000 fly ash grains,it was found that co-firing increased the formation of sticky particles by 64.8%~70.3%,resulting in a significant enhancement in capturing fine particles and Na,K vapor.Therefore,the co-firing of coal with RDF offers a promising approach to realize the harmless and resourceful treatment of municipal solid waste(MSW),and inhibit land resource losses caused by landfill.

In vitro nutrition properties of whole Tartary buckwheat straight noodles and its amelioration on type 2 diabetic rats

Dietary interventions play an important role in the prevention and treatment of type 2 diabetes(T2D).This study aims to evaluate the in vitro nutrition properties of whole Tartary buckwheat straight noodles(TSNw)and investigate its amelioration effect on T2D rats.Tartary buckwheat straight noodles(TSNs),including TSNw and TSNc(made by TB core flour),were prepared using extrusion technology,with characteristic of two times retrogradation.Results showed that TSNw presented higher in vitro antioxidant abilities and lower in vitro digestibility than TSNc(P<0.05),with significantly higher free radicals scavenging ability and lower estimated glycemic index(P<0.05).After six weeks dietary intervention,the serum metabolic level of T2D rats was determined.Results revealed that the administration of TSNs could notably reduce the level of total cholesterol,triacylglycerols,low-density lipoprotein cholesterol,glutamic-pyruvic transaminase,glutamic oxaloacetic transaminase,creatinine,urea,uric acid,and malonaldehyde,but increased the level of high-density lipoprotein cholesterol,total protein,and the activity of superoxide dismutase,and glutathione peroxidase in T2D rats.In general,the administration of TSNw presented better improvement on the complications of T2D rats than that of TSNc.This study suggests that TSNw could be a promising functional food for treating T2D.

A critical review of ash slagging mechanisms and viscosity measurement for low-rank coal and bio-slags

Gasification or combustion of coal and biomass is the most important form of power generation today.However,the use of coal/biomass at high temperatures has an inherent problem related to the ash generated.The formation of ash leads to a problematic phenomenon called slagging.Slagging is the accumulation of molten ash on the walls of the furnace,gasifier,or boiler and is detrimental as it reduces the heat transfer rate,and the combustion/gasification rate of unburnt carbon,causes mechanical failure,high-temperature corrosion and on occasions,superheater explosions.To improve the gasifier/combustor facility,it is very important to understand the key ash properties,slag characteristics,viscosity and critical viscosity temperature.This paper reviews the content,compositions,and melting characteristics of ashes in differently ranked coal and biomass,and discusses the formation mechanism,characteristics,and structure of slag.In particular,this paper focuses on low-rank coal and biomass that have been receiving increased attention recently.Besides,it reviews the available methodologies and formulae for slag viscosity measurement/prediction and summarizes the current limitations and potential applications.Moreover,it discusses the slagging behavior of different ranks of coal and biomass by examining the applicability of the current viscosity measurement methods to these fuels,and the viscosity prediction models and factors that affect the slag viscosity.This review shows that the existing viscosity models and slagging indices can only satisfactorily predict the viscosity and slagging propensity of high-rank coals but cannot predict the slagging propensity and slag viscosity of low-rank coal,and especially biomass ashes,even if they are limited to a particular composition only.Thus,there is a critical need for the development of an index,or a model or even a measurement method,which can predict/measure the slagging propensity and slag viscosity correctly for all low-rank coal and biomass ashes.