Double contrast-enhanced ultrasonography improves diagnostic accuracy of T staging compared with multi-detector computed tomography in gastric cancer patients

BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide.The disease poses a serious public health problem in China,ranking fifth for incidence and third for mortality.Knowledge of the invasive depth of the tumor is vital to treatment decisions.AIM To evaluate the diagnostic performance of double contrast-enhanced ultrasonography(DCEUS)for preoperative T staging in patients with GC by comparing with multi-detector computed tomography(MDCT).METHODS This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023.Patients underwent DCEUS,including ultrasonography(US)and intravenous contrast-enhanced ultrasonography(CEUS),and MDCT examinations for the assessment of preoperative T staging.Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual.The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard.RESULTS A total of 229 patients with GC(80 T1,33 T2,59 T3 and 57 T4)were included.Overall accuracies were 86.9%for DCEUS and 61.1%for MDCT(P<0.001).DCEUS was superior to MDCT for T1(92.5%vs 70.0%,P<0.001),T2(72.7%vs 51.5%,P=0.041),T3(86.4%vs 45.8%,P<0.001)and T4(87.7%vs 70.2%,P=0.022)staging of GC.CONCLUSION DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT,and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.

Impact of lymphatic and/or blood vessel invasion in stage Ⅱ gastric cancer

AIM： To determine the prognostic value of lymphatic and/or blood vessel invasion （LBVI） in patients with stage 11 gastric cancer. METHODS： From January 2001 to December 2006, 487 patients with histologically confirmed primary gas- tric adenocarcinoma were diagnosed with stage 11 gas- tric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node （LN） dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathologicalfindings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure （subtotal resection vs total resection）, and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS： The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years （range： 23-88 years）. The 5-year overall survival rates were 50.7% and the median survival time was 62 too. Stage Ⅱ a cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three TIN2, and stage Ⅱb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one TIN3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% （51/269） and 42.5% （71/167） in LN-negative and LN- positive patients, respectively. In 218 patients （50.0%）, there was neither a histopathologically detectable LBVI nor LN metastases （LBVI-/LN-, group I）; in 51 patients （11.7%）, LBVI with no evidence of LN me- tastases was detected （LBVILN-, group 11）. In 167 patients （38.3%）, LN metastases were found. Among those patients, LBVI was not determined in 96 patients （22.0%） （LBVI-γLN, group Ⅲ）, and was determined in 71 patients （16.3%） （LBVI＋LN＋, group Ⅳ）. Correla- tion analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI （P 〈 0.001）. The overall 5-year sur- vival was significantly longer in LN-negative patients compared with LN-positive patients （56.1% vs 42.3%, P = 0.015）. There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI- negative tumors （39.6% vs 54.8%, P = 0.006）. Overall 5-year survival rates in each group were 58.8% （ Ⅰ）, 45.8% （Ⅱ）, 45.7% （Ⅲ） and 36.9% （Ⅳ）, and there was a significant difference in overall survival between the four groups （P=-0.009）. Multivariate analysis in stage 11 gastric cancer patients revealed that LBVI in- dependently affected patient prognosis in LN-negativepatients （P = 0.018） but not in LN-positive patients （P = 0.508）. CONCLUSION： In LN-negative stage 11 gastric cancer patients, LBVI is an additional independent prognostic markeF, and may provide useful information to identify patients with poorer prognosis.

Operative link on gastritis assessment stage is an appropriate predictor of early gastric cancer

AIM: To assess the predictive value of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages in gastric cancer.METHODS: A prospective study was conducted with 71 patients with early gastric cancer (EGC) and 156 patients with non-EGC. All patients underwent endoscopic examination and systematic biopsy. Outcome measures were assessed and compared, including the Japanese endoscopic gastric atrophy (EGA) classification method and the modified OLGA method as well as the modified OLGIM method. Helicobacter pylori (H. pylori) status was determined for all study participants. Stepwise logistic regression modeling was performed to analyze correlations between EGC and the EGA, OLGA and OLGIM methods.RESULTS: For patients with EGC and patients with non-EGC, the proportions of moderate-to-severe EGA cases were 64.8% and 44.9%, respectively (P = 0.005), the proportions of OLGA stages III-IV cases were 52.1% and 22.4%, respectively (P &#x0003c; 0.001), and the proportions of OLGIM stages III-IV cases were 42.3% and 19.9%, respectively (P &#x0003c; 0.001). OLGA stage and OLGIM stage were significantly related to EGA classification; specifically, logistic regression modeling showed significant correlations between EGC and moderate-to-severe EGA (OR = 1.95, 95% CI: 1.06-3.58, P = 0.031) and OLGA stages III-IV (OR = 3.14, 95%CI: 1.71-5.81, P &#x0003c; 0.001), but no significant correlation between EGC and OLGIM stages III-IV (P = 0.781). H. pylori infection rate was significantly higher in patients with moderate-to-severe EGA (75.0% vs 54.1%, P = 0.001) or OLGA/OLGIM stages III-IV (OLGA: 83.6% vs 55.8%, P &#x0003c; 0.001; OLGIM: 83.6% vs 57.8%, P &#x0003c; 0.001).CONCLUSION: OLGA classification is optimal for EGC screening. A surveillance program including OLGA stage and H. pylori infection status may facilitate early detection of gastric cancer.

Prognostic factors in stage IB gastric cancer

AIM:To identify the subset of patients with stage IB gastric cancer with an unfavorable prognosis.METHODS:Overall survival(OS)rates were examined in 103 patients with stage IB(T1N1M0 and T2N0M0)gastric cancer between January 2000 and December2011.Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model.RESULTS:The OS rates of patients with T1N1 and T2N0 cancer were 89.2%and 94.1%at 5-years,re-spectively.Both univariate and multivariate analyses demonstrated that tumor location was the only significant prognostic factor.The OS rate was 81.8%at5-years when the tumor was located in the upper third of the stomach and was 95.5%at 5-years when the tumor was located in the middle or lower third of the stomach(P=0.0093).CONCLUSION:These data may suggest that tumor location is associated with survival in patients with stage IB gastric cancer.

Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer

AIM： To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer. METHODS： Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals. Allelic discrimination was performed by quantitative real-time polymerase chain reaction. Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression. RESULTS： Thirty-nine （32%） patients displayed a CC genotype, 57 （46.7%） a CT genotype and 26 （21.3%） a TT genotype. The frequency of the C allele （fC） in the patient group was 0.55, which was not significantly different from that of healthy blood donors. The distribution was compatible with the Hardy-Weinberg equilibrium. Analysis of clinicopathological parameters did not show any significant correlation of the T393C genotype with gender （P = 0.50）, differentiation （P = 0.29）, pT-category （P = 0.19）, pN-category （P = 0.30）, pM-category （P = 0.25）, R-category （P = 0.95）, the classifications according to WHO （P = 0.34）, Lauren （P = 0.16）, Goseki （P = 1.00） and Ming （P =0.74）. Dichotomization between C＋ （CC＋CT） and C-genotypes （FI）, however, revealed significantly more advanced tumor stages （P = 0.023） and lower survival rates （P = 0.043） for C allele carriers. CONCLUSION： The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers.

Roux-en-Y versus BillrothⅠreconstruction after distal gastrectomy for gastric cancer:A meta-analysis

AIM: To conduct a meta-analysis to compare Roux-en-Y (R-Y) gastrojejunostomy with gastroduodenal Billroth?I?(B-I) anastomosis after distal gastrectomy (DG) for gastric cancer.METHODS: A literature search was performed to identify studies comparing R-Y with B-I?after DG for gastric cancer from January 1990 to November 2012 in Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in The Cochrane Library. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either ?xed or random effects model. Operative outcomes such as operation time, intraoperative blood loss and postoperative outcomes such as anastomotic leakage and stricture, bile re?ux, remnant gastritis, re?ux esophagitis, dumping symptoms, delayed gastric emptying and hospital stay were the main outcomes assessed. Meta-analyses were performed using RevMan 5.0 software (Cochrane library).RESULTS: Four randomized controlled trials (RCTs) and 9 non-randomized observational clinical studies (OCS) involving 478 and 1402 patients respectively were included. Meta-analysis of RCTs revealed that R-Y reconstruction was associated with a reduced bile re?ux (OR 0.04, 95%CI: 0.01, 0.14; P < 0.00?001) and remnant gastritis (OR 0.43, 95%CI: 0.28, 0.66; P = 0.0001), however needing a longer operation time (WMD 40.02, 95%CI: 13.93, 66.11; P = 0.003). Meta-analysis of OCS also revealed R-Y reconstruction had a lower incidence of bile re?ux (OR 0.21, 95%CI: 0.08, 0.54; P = 0.001), remnant gastritis (OR 0.18, 95%CI: 0.11, 0.29; P < 0.00?001) and re?ux esophagitis (OR 0.48, 95%CI: 0.26, 0.89; P = 0.02). However, this reconstruction method was found to be associated with a longer operation time (WMD 31.30, 95%CI: 12.99, 49.60; P = 0.0008).CONCLUSION: This systematic review point towards some clinical advantages that are rendered by R-Y compared to B-I?reconstruction post DG. However there is a need for further adequately powered, well-designed RCTs comparing the same.

Macroscopic appearance of TypeⅣand giant Type Ⅲ is a high risk for a poor prognosis in pathological stage Ⅱ/Ⅲ advanced gastric cancer with postoperative adjuvant chemotherapy

AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.

Analysis of vascular thrombus and clinicopathological factors in prognosis of gastric cancer:A retrospective cohort study

BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors in the world,and its prognosis is closely related to many factors.In recent years,the incidence of vascular thrombosis in patients with GC has gradually attracted increasing attention,and studies have shown that it may have a significant impact on the survival rate and prognosis of patients.However,the specific mechanism underlying the association between vascular thrombosis and the prognosis of patients with GC remains unclear.AIM To analyze the relationships between vascular cancer support and other clinicopathological factors and their influence on the prognosis of patients with GC.METHODS This study retrospectively analyzed the clinicopathological data of 621 patients with GC and divided them into a positive group and a negative group according to the presence or absence of a vascular thrombus.The difference in the 5-year cumulative survival rate between the two groups was compared,and the relationships between vascular cancer thrombus and other clinicopathological factors and their influence on the prognosis of patients with GC were analyzed.RESULTS Among 621 patients with GC,the incidence of vascular thrombi was 31.7%(197 patients).Binary logistic regression analysis revealed that the degree of tumor differentiation,depth of invasion,and extent of lymph node metastasis were independent influencing factors for the occurrence of vascular thrombi in GC patients(P<0.01).The trend of the χ^(2) test showed that the degree of differentiation,depth of invasion,and extent of lymph node metastasis were linearly correlated with the percentage of vascular thrombi in GC patients(P<0.01),and the correlation between lymph node metastasis and vascular thrombi was more significant(r=0.387).Univariate analysis revealed that the 5-year cumulative survival rate of the positive group was significantly lower than that of the negative group(46.7%vs 73.3%,P<0.01).Multivariate analysis revealed that age,tumor diameter,TNM stage,and vascular thrombus were independent risk factors for the prognosis of GC patients(all P<0.05).Further stratified analysis revealed that the 5-year cumulative survival rate of stage Ⅲ GC patients in the thrombolase-positive group was significantly lower than that in the thrombolase-negative group(36.1%vs 51.4%;P<0.05).CONCLUSION Vascular cancer status is an independent risk factor affecting the prognosis of patients with GC.The combination of vascular cancer suppositories and TNM staging can better judge the prognosis of patients with GC and guide more reasonable treatment.

Clinical application of oral contrast-enhanced ultrasound in evaluating the preoperative T staging of gastric cancer

BACKGROUND Oral contrast-enhanced ultrasound(OCEUS)is widely used in the noninvasive diagnosis and screening of gastric cancer(GC)in China.AIM To investigate the clinical application of OCEUS in evaluating the preoperative T staging of gastric cancer.METHODS OCEUS was performed before the operation,and standard ultrasound images were retained.The depth of infiltration of GC(T-stage)was evaluated according to the American Joint Committee on Cancer 8th edition of the tumor-nodemetastasis staging criteria.Finally,with postoperative pathological staging as the gold standard reference,the sensitivity,specificity,negative predictive value,positive predictive value,and diagnostic value of OCEUS T staging were evaluated.RESULTS OCEUS achieved diagnostic accuracy rates of 76.6%(T1a),69.6%(T1b),62.7%(T2),60.8%(T3),88.0%(T4a),and 88.7%(T4b),with an average of 75.5%.Ultrasonic T staging sensitivity exceeded 62%,aside from T1b at 40.3%,while specificity was over 91%,except for T3 with 83.5%.The Youden index was above 60%,with T1b and T2 being exceptions.OCEUS T staging corresponded closely with pathology in T4b(kappa>0.75)and moderately in T1a,T1b,T2,T3,and T4a(kappa 0.40-0.75),registering a concordance rate exceeding 84%.CONCLUSION OCEUS was effective,reliable,and accurate in diagnosing the preoperative T staging of GC.As a noninvasive diagnostic technique,OCEUS merits clinical popularization.

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

Accurate prediction of lymph node(LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer(EGC). However,consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search,we identified several independent variables associated with LN metastasis in EGC,which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand,even if we use these promising parameters,we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN(SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review,we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition,we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.

Long-term survival of patients with stage Ⅱ and Ⅲgastric cancer who underwent gastrectomy with inadequate nodal assessment

BACKGROUND Gastric cancer is an aggressive disease with frequent lymph node(LN)involvement.The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs.This threshold has been the subject of great debate,not only for the extent of surgery but also for more appropriate staging.The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer(AJCC)staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number.Furthermore,studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastriccancer.AIM To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation.METHODS Eligible patients were identified from the Surveillance,Epidemiology,and End Results database.Those with stage II-III gastric cancer were considered for inclusion.Three groups were compared based on the number of analyzed LNs.They were inadequate LN assessment(ILA,<16 LNs),adequate LN assessment(ALA,16-29 LNs),and optimal LN assessment(OLA,≥30 LNs).The main outcomes were overall survival(OS)and cancer-specific survival.Data were analyzed by the Kaplan-Meier product-limit method,log-rank test,hazard risk,and Cox proportional univariate and multivariate models.Propensity score matching(PSM)was used to compare the ALA and OLA groups.RESULTS The analysis included 11607 patients.Most had advanced T stages(T3=48%;T4=42%).The pathological AJCC stage distribution was IIA=22%,IIB=18%,IIIA=26%,IIIB=22%,and IIIC=12%.The overall sample divided by the study objective included ILA(50%),ALA(35%),and OLA(15%).Median OS was 24 mo for the ILA group,29 mo for the ALA group,and 34 mo for the OLA group(P<0.001).Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group[ALA hazard ratio(HR)=0.84,95%confidence interval(CI):0.79-0.88,P<0.001 and OLA HR=0.73,95%CI:0.68-0.79,P<0.001].The OS outcome was confirmed by multivariate analysis(ALA HR=0.68,95%CI:0.64-0.71,P<0.001 and OLA:HR=0.48,95%CI:0.44-0.52,P<0.001).A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group(OS:OLA median=34 mo vs ALA median=26 mo,P<0.001,which was confirmed by univariate analysis(HR=0.81,95%CI:0.75-0.89,P<0.001)and multivariate analysis:(HR=0.71,95%CI:0.65-0.78,P<0.001).CONCLUSION Proper nodal staging is a critical issue in gastric cancer.Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.

Effects of small interfering RNA inhibit Class Ⅰ phosphoinositide 3-kinase on human gastric cancer cells

AIM: To investigate the effects of small interfering RNA (siRNA)-mediated inhibition of Class?I?phosphoinositide 3-kinase (Class?I?PI3K) signal transduction on the proliferation, apoptosis, and autophagy of gastric cancer SGC7901 and MGC803 cells.METHODS: We constructed the recombinant replication adenovirus PI3K(I)-RNA interference (RNAi)-green fluorescent protein (GFP) and control adenovirus NC-RNAi-GFP, and infected it into human gastric cancer cells. MTT assay was used to determine the growth rate of the gastric cancer cells. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after adenovirus PI3K(I)-RNAi-GFP and control adenovirus NC-RNAi-GFP treatment. Immunofluorescence staining was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. The expression of autophagy was monitored with MDC, LC3 staining, and transmission electron microscopy. Western blotting was used to detect p53, Beclin-1, Bcl-2, and LC3 protein expression in the culture supernatant.RESULTS: The viability of gastric cancer cells was inhibited after siRNA targeting to the Class?I?PI3K blocked Class?I?PI3K signal pathway. MTT assays revealed that, after SGC7901 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 27.48% ± 2.71% at 24 h, 41.92% ± 2.02% at 48 h, and 50.85% ± 0.91% at 72 h. After MGC803 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 24.39% ± 0.93% at 24 h, 47.00% ± 0.87% at 48 h, and 70.30% ± 0.86% at 72 h (P < 0.05 compared to control group). It was determined that when 50 MOI, the transfection efficiency was 95% ± 2.4%. Adenovirus PI3K(I)-RNAi-GFP (50 MOI) induced mitochondrial dysfunction and activated cell apoptosis in SGC7901 cells, and the results described here prove that RNAi of Class?I?PI3K induced apoptosis in SGC7901 cells. The results showed that adenovirus PI3K(I)-RNAi-GFP transfection induced punctate distribution of LC3 immunoreactivity, indicating increased formation of autophagosomes. The results showed that the basal level of Beclin-1 and LC3 protein in SGC7901 cells was low. After incubating with adenovirus PI3K(I)-RNAi-GFP (50 MOI), Beclin-1, LC3, and p53 protein expression was significantly increased from 24 to 72 h. We also found that Bcl-2 protein expression down-regulated with the treatment of adenovirus PI3K(I)-RNAi-GFP (50 MOI). A number of isolated membranes, possibly derived from ribosome-free endoplasmic reticulum, were seen. These isolated membranes were elongated and curved to engulf a cytoplasmic fraction and organelles. We used transmission electron microscopy to identify ultrastructural changes in SGC7901 cells after adenovirus PI3K(I)-RNAi-GFP (50 MOI) treatment. Control cells showed a round shape and contained normal-looking organelles, nucleus, and chromatin, while adenovirus PI3K(I)-RNAi-GFP (50 MOI)-treated cells exhibited the typical signs of autophagy.CONCLUSION: After the Class?I?PI3K signaling pathway has been blocked by siRNA, the proliferation of cells was inhibited and the apoptosis of gastric cancer cells was enhanced.

High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients

BACKGROUND Gastric cancer(GC)remains an aggressive malignancy with a high rate of mortality,being the third leading cause of cancer-related death.More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018.GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients.The discovery of new biomarkers useful in the early diagnosis of GC is mandatory.AIM To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.METHODS Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1.Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue.The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients.Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.RESULTS Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue(P<0.05).COL10A1 seems to show an elevated expression from the beginning of carcinogenesis,in the early stages,and its increased level remains elevated during cancer progression.A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified.Moreover,increased COL10A1 plasma level was associated with poor survival of the patients.Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve(AUC)of 0.9171(P=0.0002),sensitivity of 87.76%,and specificity of 100.0%.Furthermore,this study demonstrated the potential role of plasma COL10A1 in the early detection of GC,as in the early stage,we obtained an AUC of 0.8789(P=0.0030),sensitivity of 81.25%,and specificity of 100.0%.CONCLUSION Circulating expression level of COL10A1 is significantly increased in gastric adenocarcinoma patients being associated with poor survival and is a potential biomarker for early detection of GC.

Isolated vaginal metastasis from stage Ⅰ colon cancer: A case report

BACKGROUND Distant metastasis occasionally occurs in patients who have been diagnosed with colorectal cancer(CRC), but it occurs in a few patients with stage I CRC. The vagina as a metastasis site has also been reported, albeit rarely. Most reported cases of vaginal metastasis(VM) report their origin from advanced CRC. We encountered a patient who was diagnosed with isolated VM originating from stage I colon cancer(T2N0) and herein present the case of this patient.CASE SUMMARY A 63-year-old woman visited the outpatient clinic because of a positive result from a stool occult blood test. She underwent laparoscopic anterior resection and was pathologically diagnosed with stage I(T2N0) sigmoid colon cancer. Neither lymphovascular invasion nor perineural invasion was observed. Ten months following the surgery, isolated vaginal metastases were detected on gynecologic examination. The examination was performed due to vaginal spotting. A transvaginal wide excision was performed, and no other adjuvant treatment was provided after discussion with a multidisciplinary team and the patient.Subsequently, a new VM was discovered after 33 mo. An additional transvaginal excision was performed. To date, there has been no evidence of further disease progression. From the time of diagnosis of VM, the patient’s overall survival has been 54 mo.CONCLUSION VM can occur as a result of early-stage colorectal cancer. Surgeons should consider the possibility of VM following complaints of gynecologic symptoms following surgery.

Value of serum pepsinogenⅠ andⅡ ratio for evaluating the malignant biological behaviors in gastric cancer lesions

Objective:To study the value of serum pepsinogenⅠ andⅡ ratio (PGR) for evaluating the malignant biological behaviors in gastric cancer lesions.Methods:The patients with gastric cancer who underwent radical surgery in 363 Hospital between July 2015 and February 2018 were selected as the gastric cancer group in the study, and the volunteers who had physical examination in 363 Hospital during the same period were selected as the control group. Serum was collected to measure pepsinogenⅠ and pepsinogenⅡ and then calculate the PGR;gastric cancer lesions were collected to measure the expression of oncogenes and angiogenesis genes.Results:Serum PGR level of the gastric cancer group was significantly lower than that of the control group, serum PGR level of the patients with moderately-highly differentiated gastric cancer was significantly higher than that of the patients with lowly differentiated gastric cancer, serum PGR level of the patients with TNM stage III gastric cancer was significantly lower than that of the patients with TNM stage I+II gastric cancer, and serum PGR level of the gastric cancer patients with lymph node metastasis was significantly lower than that of the gastric cancer patients without lymph node metastasis;PGR=3.8 was taken as the cutoff point, and p53 and TXNIP mRNA expression in the lesions of the gastric cancer patients with PGR < 3.8 were significantly lower than those of the gastric cancer patients with PGR > 3.8 while Bcl-2,β-catenin, Survivin, COX-2, HIF-1α, VEGF, c-Met and CNPY2 mRNA expression were significantly higher than those of the gastric cancer patients with PGR > 3.8.Conclusion:The decrease of PGR in serum of patients with gastric cancer is valuable for evaluating the pathological process and malignant biological behaviors.

Recent advances in conversion therapy schemes for stage Ⅳ gastric cancer

“Conversion therapy”is a treatment modality that involves the use of radiotherapy,chemotherapy,targeted therapy,immunotherapy,and other therapeutic methods to transform initially late-stage tumors that cannot be cured into treatments that can achieve an R0 curative effect.However,selecting an appropriate conversion therapy scheme remains a challenge,and there are currently few relevant studies on this topic.This article reviews successful cases of conversion therapy and clinical studies on treatment schemes,at domestic and international levels,over the past few years to offer a broad range of treatment options for patients.

Correlation of serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation of cancer cells in patients with gastric cancer

Objective: To investigate the correlation of serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation of cancer cells in patients with gastric cancer. Methods:Superficial gastritis group (n=247), gastric ulcer group (n=159) and gastric cancer group (n=97) who were pathologically diagnosed by gastroscopy in Chongqing wanzhou district people's hospital of 5 between August 2016 and August 2017 were selected, and the differences in serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content as well as proliferation and apoptosis gene expression in lesion tissue were compared among the three groups. Pearson test was used to evaluate the correlation of pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation activity of cancer cells in patients with gastric cancer. Results: Serum pepsinogenⅠ/Ⅱ ratio and gastrin-17 content in gastric cancer group were lower than those in gastric ulcer group and superficial gastritis group. Proliferation genes EIF5A2, MACF1 and PIK3CD mRNA expression levels in gastric cancer group were higher than those in gastric ulcer group and superficial gastritis group whereas SIRT1 mRNA expression level was lower than that in gastric ulcer group and superficial gastritis group;apoptosis gene Livin mRNA expression level was higher than that in gastric ulcer group and superficial gastritis group whereas Bad and Noxa mRNA expression levels were lower than those in gastric ulcer group and superficial gastritis group;serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content in gastric cancer group were negatively correlated with EIF5A2, MACF1, PIK3CD and Livin mRNA expression levels, and positively correlated with SIRT1, Bad and Noxa mRNA expression levels. Conclusion: The serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content abnormally reduce in patients with gastric cancer, and the specific levels are directly correlated with gastric cancer cell proliferation and apoptosis activity.

皖南蝮蛇毒抑瘤组分-Ⅰ对胃癌MKN-28细胞增殖、迁移及凋亡的影响

目的:探讨皖南蝮蛇毒抑瘤组分-Ⅰ(agkistrodon halys venom antitumor componentⅠ,AHVAC-Ⅰ)对胃癌MKN-28细胞生物学行为的影响作用。方法:不同实验浓度(5、10和15μg/mL)AHAVC-Ⅰ处理胃癌细胞MKN-2824 h后,采用细胞增殖和毒性检测(cell counting kit-8,CCK-8)法检测细胞增殖活力;划痕实验和Tanswell小室检测细胞迁移能力;激光共聚焦显微镜(annexin VmCherry/DAPI双染)和流式细胞术(annexin VFITC/PI双染)检测细胞凋亡;Western blot检测细胞凋亡相关蛋白Caspease-3的表达水平。结果:AHVAC-Ⅰ各浓度组分别与正常对照组相比结果显示,随着AHVAC-Ⅰ浓度的增加,MKN-28细胞增殖活力逐渐下降(P<0.01),细胞迁移能力逐渐被抑制(P<0.01),细胞凋亡率增高(P<0.05),凋亡相关蛋白Caspease-3表达上调(P<0.01)。结论:AHVAC-Ⅰ抑制胃癌细胞MKN-28增殖和迁移,诱导其凋亡。

New approaches to gastric cancer staging:Beyond endoscopic ultrasound,computed tomography and positron emission tomography

Currently, there is no single gold standard modality for staging of gastric cancer and several methods have been used complementarily in the each clinical situation. To make up for the shortcomings of conventional modalities such as endoscopic ultrasound, computed tomography and 18F-fluoro-2-deoxyglucose positron emission tomography, numerous attempts with new approaches have been made for gastric cancer staging. For T staging, magnifying endoscopy with narrow-band was evaluated to differentiate mucosal cancer from submucosal cancer. Single/double contrast-enhanced ultrasound and diffusion-weighted magnetic resonance imaging were also tried to improve diagnostic accuracy of gastric cancer. For intraoperative staging with sentinel node mapping, indocyanine green infrared and fluorescence imaging was introduced. In addition, to detect micrometastasis, real-time reverse transcription-polymerase chain reaction system with multiple markers was studied. Staging laparoscopy using 5-aminolevulinic acid-mediated photodynamic diagnosis and percutaneous diagnostic peritoneal lavage were also evaluated. However, most studies reporting new staging methods is preliminary and further studies for validation in clinical practice are needed. In this mini-review, we discuss new progress in gastric cancer staging. Especially, we focus on new diagnostic approach to gastric cancer staging beyond the conventional modalities and briefly review the remarkable clinical results of the studies published over the past three years.

Usefulness of endoscopic ultrasonography in preoperative TNM staging of gastric cancer

AIM： To evaluate the value of endoscopic ultrasono- graphy （EUS） in the preoperative TNM staging of gastric cancer. METHODS ： Forty-one patients with gastric cancer （12 early stage and 29 advanced stage） proved by esophagogastroduodenoscopy and biopsies preoperatively evaluated with EUS according to TNM （1997） classification of International Union Contrele Cancer （UICC）. Pentax EG-3630U/Hitachi EUB-525 echo endoscope with real-time ultrasound imaging linear scanning transducers （7.5 and 5.0 MHz） and Doppler information was used in the current study. EUS staging procedures for tumor depth of invasion （T stage） were performed according to the widely accepted five-layer structure of the gastric wall. All patients underwent surgery. Diagnostic accuracy of EUS for TNM staging of gastric cancer was determined by comparing preoperative EUS with subsequent postoperative histopathologic findings. RESULTS： The overall diagnostic accuracy of EUS in preoperative determination of cancer depth of invasion was 68.3% （41/28） and 83.3% （12/10）, 60% （20/12）, 100% （5/5）, 25% （4/1） for T1, T2, T3, and T4, respectively. The rates for overstaging and understaging were 24.4% （41110）, and 7.3% （4113）, respectively. EUS tended to overstage T criteria, and main reasons for overstaging were thickening of the gastric wall due to perifocal inflammatory change, and absence of serosal layer in certain areas of the stomach. The diagnostic accuracy of metastatic lymph node involvement or N staging of EUS was 100% （17/17） for NO and 41.7% （24/10） for N＋, respectively, and 66% （41127） overall.Misdiagnosing of the metastatic lymph nodes was related to the difficulty of distinguishing inflammatory lymph nodes from malignant lymph nodes, which imitate similar echo features. Predominant location and distribution of tumors in the stomach were in the antrum （20 patients）, and the lesser curvature （17 patients）, respectively. Three cases were found as surgically unresectable （T4 N＋）, and included as being correctly diagnosed by EUS. CONCLUSION： EUS is a useful diagnostic method for preoperative staging of gastric cancer for T and N criteria. However, EUS evaluation of malignant lymph nodes is still unsatisfactory.