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.

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.

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.

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.

Carcinoembryonic antigen,carbohydrate antigen 199 and carbohydrate antigen 724 in gastric cancer and their relationship with clinical prognosis

BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the diseases caused by abnormal gene changes,GC has abnormal expression of various oncogenes and products during its development.Tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)are not expressed or lowly expressed in normal people,but significantly increased after carcinogenesis.Monitoring the changes in the levels of tumor markers such as CEA,CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors.AIM To investigate the expression of CEA,CA199 and CA724 in GC and their correlation with clinical features,hoping to provide more effective markers for the early preventive diagnosis of GC.METHODS Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group,and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group.The serum CEA,CA199,and CA724 levels were compared between the two groups,and the serum CEA,CA199,and CA724 levels were compared in patients with GC at different TNM stages,and the differences in the positive rates of CEA,CA199,and CA724 alone and in combination in detecting TNM stages of GC and GC were compared.In addition,the relationship between the levels of tumor markers CEA,CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed.The relationship between the serum levels of CEA,CA199 and CA724 and the survival period of GC patients was analyzed by Pearson.RESULTS The serum levels of CEA,CA199 and CA724 in GC group were significantly higher than those in control group(P<0.05).With the increase of TNM stage,the serum CEA,CA199 and CA724 expression levels in GC patients increased significantly,and the differences between groups were statistically significant(P<0.05).The positive rate of the CA724 single test was higher than that of CEA and CA199 single test(P<0.05).The positive rate of the three combined tests was 95.40%(83/87),which was higher than that of CEA,CA199 and CA724 single tests.The difference was statistically significant(P<0.05).The combined detection positive rates of CEA,CA199,and CA724 in stages I,II,III,and IV of GC were 89.66%,93.10%,98.85%,and 100.00%respectively,all of which were higher than the individual detection rates of CEA,CA199,and CA724.The differences were statistically significant(P<0.05).There was no significant difference in serum CEA,CA199 and CA724 levels between GC patients with different genders,smoking history and alcohol history(P>0.05).However,the serum CEA,CA199 and CA724 levels were significantly higher in GC patients aged≥45 years,TNM stage III-IV,with lymph node metastasis and tumor diameter≥5 cm than in GC patients aged<45 years,TNM stage I-II,without lymph node metastasis and tumor diameter<5 cm(P<0.05).CONCLUSION The expression levels of serum tumor markers CEA,CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage.The levels of CEA,CA199 and CA724 are related to age,TNM stage,lymph node metastasis and tumor diameter.The combined detection of CEA,CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.

Incorporation of perigastric tumor deposits into the TNM staging system for primary gastric cancer

BACKGROUND The current prognostic significance of perigastric tumor deposits(TDs)in gastric cancer(GC)remains unclear.AIM To assess the prognostic value of perigastric TDs and put forward a new TNM staging framework involving TDs for primary GC.METHODS This study retrospectively analyzed the pathological data of 6672 patients with GC who underwent gastrectomy or surgery for GC with other diseases from January 1,2012 to December 31,2017 at the Chinese PLA General Hospital.According to the presence of perigastric TDs or not,the patients were divided into TD-positive and TD-negative groups by using the method of propensity score matching.The differences between TD-positive and TD-negative patients were analyzed using binary logistic regression modeling.The Kaplan-Meier method was used to plot survival curves.Multivariate Cox regression modeling and the log-rank test were used to analyze the data.RESULTS Perigastric TDs were found to be positive in 339(5.09%)of the 6672 patients with GC,among whom 237 were men(69.91%)and 102 were women(30.09%)(2.32:1).The median age was 59 years(range,27 to 78 years).Univariate and multivariate survival analyses indicated that TD-positive GC patients had a poorer prognosis than TD-negative patients(P<0.05).The 1-,3-,and 5-year overall survival rates of GC patients with TDs were 68.3%,19.6%,and 11.2%,respectively,and these were significantly poorer than those without TDs of the same stages.There was significant variation in survival according to TD locations among the GC patients(P<0.05).A new TNM staging framework for GC was formulated according to TD location.When TDs appear in the gastric body,the original stages T1,T2,and T3 are classified as T4a with the new framework,and the original stages T4a and T4b both are classified as T4b.When TDs appear in the lesser curvature,the previous stages N0,N1,N2,and N3 now both are classified as N3.When TDs appear in the greater curvature or the distant tissue,the patient should be categorized as having M1.With the new GC staging scheme including TDs,the survival curves of patients in the lower grade TNM stage with TDs were closer to those of patients in the higher grade TNM stage without TDs.CONCLUSION TDs are a poor prognostic factor for patients with primary GC.The location of TDs is associated with the prognosis of patients with primary GC.Accordingly,we developed a new TNM staging framework involving TDs that is more appropriate for patients with primary GC.

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.

Prophylactic lateral pelvic lymph node dissection in stage Ⅳ low rectal cancer

AIM To assess the clinical significance of prophylactic lateral pelvic lymph node dissection (LPLND) in stage Ⅳ low rectal cancer.METHODS We selected 71 consecutive stage Ⅳ low rectal cancer patients who underwent primary tumor resection,and enrolled 50 of these 71 patients without clinical LPLN metastasis.The patients had distant metastasis such as liver,lung,peritoneum,and paraaortic LN.Clinical LPLN metastasis was defined as LN with a maximum diameter of 10 mm or more on preoperative pelvic computed tomography scan.All patients underwent primary tumor resection,27 patients underwent total mesorectal excision(TME) with LPLND(LPLND group),and 23 patients underwent only TME(TME group).Bilateral LPLND was performed simultaneously with primary tumor resection in LPLND group.R0 resection of both primary and metastatic sites was achieved in 20 of 50 patients.We evaluated possible prognostic factors for 5-year overall survival (OS),and compared 5-year cumulative local recurrence between the LPLND and TME groups.RESULTS For OS,univariate analyses revealed no significant benefit in the LPLND compared with the TME group (28.7% vs 17.0%,P = 0.523); multivariate analysis revealed that R0 resection was an independent prognostic factor.Regarding cumulative local recurrence,the LPLND group showed no significant benefit compared with TME group (21.4% vs 14.8%,P = 0.833).CONCLUSION Prophylactic LPLND shows no oncological benefits in patients with Stage Ⅳ low rectal cancer without clinical LPLN metastasis.

Radical treatment of stage Ⅳ pancreatic cancer by the combination of cryosurgery and iodine-125 seed implantation

AIM:To investigate the therapeutic effect of radical treatment and palliative treatment in stage Ⅳ pancreatic cancer patients.METHODS:81 patients were enrolled in the study.Radical treatment was performed on 51 patients,while 30 patients were put under palliative treatment.The procedural safety and interval survival for stage Ⅳ pancreatic cancer(IS-Ⅳ) was assessed by almost 2.5 years of follow-ups.The IS-Ⅳ of patients under the two kinds of treatment,and the effects of treatment timing and frequency on IS-Ⅳ,were compared.RESULTS:The IS-Ⅳ of patients who received radical treatment was significantly longer than those who received palliative treatment(P < 0.001).The IS-Ⅳ of patients who received delayed radical or palliative treatment was longer than those who received accordingly timely treatment(P = 0.0034 and 0.0415,respectively).Multiple treatments can play an important role in improving the IS-Ⅳ of patients who received radical treatment(P = 0.0389),but not for those who received palliative treatment(P = 0.99).CONCLUSION:The effect of radical treatment was significantly more obvious than that of palliative treatment,and multiple radical treatments may contribute more to patients than a single radical treatment.

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.

Astragaloside Ⅳ inhibits pathological functions of gastric cancer-associated fibroblasts

AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gastric cancer-associated fibroblast(GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside Ⅳ. Conditioned media were prepared from GNFs,GCAFs,control-treated GCAFs,and astragaloside Ⅳ-treated GCAFs,and used to culture BGC-823 human gastric cancer cells. Proliferation,migration and invasion capacities of BGC-823 cells were determined by MTT,wound healing,and Transwell invasion assays,respectively. The action mechanism of astragaloside Ⅳ was investigated by detecting the expression of micro RNAs and the expression and secretion of the oncogenic factor,macrophage colonystimulating factor(M-CSF),and the tumor suppressive factor,tissue inhibitor of metalloproteinase 2(TIMP2),in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined.RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P < 0.01). Astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P < 0.05 for 10 μmol/L,P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs,GCAFs expressed a lower level of micro RNA-214(P < 0.01) and a higher level of micro RNA-301 a(P < 0.01). Astragaloside Ⅳ treatment significantly upregulated micro RNA-214 expression(P < 0.01) and down-regulated micro RNA-301 a expression(P < 0.01) in GCAFs. Reestablishing the micro RNA expression balance subsequently suppressed M-CSF production(P < 0.01) and secretion(P < 0.05),and elevated TIMP2 production(P < 0.01) and secretion(P < 0.05). Consequently,the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside Ⅳ.CONCLUSION Astragaloside Ⅳ can inhibit the pathological functions of GCAFs by correcting their dysregulation of micro RNA expression,and it is promisingly a potent therapeutic agent regulating tumor microenvironment.

Subtotal gastrectomy combined with chemotherapy: An effective therapy for patients with circumscribed Borrmann type Ⅳ gastric cancer

BACKGROUND Although Borrmann type Ⅳ(B-4) gastric cancer has a higher mortality rate and presents distant metastasis easily, especially peritoneal metastasis, when diagnosed, some B-4 patients were found to have no distant metastasis by preoperative detection and underwent curative surgery, which was defined as circumscribed B-4 in our study. In this study, we focused on the circumscribed B-4 patients without distant metastasis during surgery to identify factors related to prognosis and postoperative peritoneal cavity metastasis(PPCM), which is important for selecting an appropriate therapeutic strategy.AIM To identify factors related to the prognosis and PPCM of B-4 patients.METHODS A total of 117 B-4 patients who underwent gastrectomy between January 2005 and December 2012 were included in this study. Survival analysis was performed using Kaplan–Meier analysis and Cox multivariate models. Pearson correlation analyses were performed to identify the factors related to PPCM. All statistical analyses were performed using SPSS 20.0.RESULTS Lymph node status, gastrectomy type, and postoperative chemotherapy were independent prognostic factors in 117 circumscribed B-4 patients. Subtotal gastrectomy combined with chemotherapy could significantly improve the longterm survival time. Six patients who were diagnosed with pN0 and received the combination therapy had a 3-year survival rate of 100% and a median survival of 77.7 mo. Even for patients with metastatic lymph nodes(n = 13), the combination therapy also increased the 3-year overall survival rate to 57.1%. In addition, positive lymph node status was the only factor(P = 0.005) correlated with PPCM in certain B-4 patients, and chemotherapy was useful for suppressing PPCM in patients with subtotal gastrectomy but not in those with total gastrectomy.CONCLUSION Lymph node status is an independent prognostic factor for circumscribed B-4 patients. In addition, subtotal gastrectomy and postoperative chemotherapy could effectively improve prognosis and even suppress PPCM.

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.

Systematic review of diagnostic tools for peritoneal metastasis in gastric cancer-staging laparoscopy and its alternatives

BACKGROUND Gastric cancer is one of the leading causes of cancer burden and mortality,often resulting in peritoneal metastasis in advanced stages with negative survival outcomes.Staging laparoscopy has become standard practice for suspected cases before a definitive gastrectomy or palliation.This systematic review aims to compare the efficacy of other diagnostic modalities instead of staging laparoscopy as the alternatives are able to reduce cost and invasive staging procedures.Recently,a radiomic model based on computed tomography and positron emission tomography(PET)has also emerged as another method to predict peritoneal metastasis.AIM To determine if the efficacy of computed tomography,magnetic resonance imaging and PET is comparable with staging laparoscopy.METHODS Articles comparing computed tomography,PET,magnetic resonance imaging,and radiomic models based on computed tomography and PET to staging laparoscopies were filtered out from the Cochrane Library,EMBASE,PubMed,Web of Science,and Reference Citations Analysis(https://www.referencecitationanalysis.com/).In the search for studies comparing computed tomography(CT)to staging laparoscopy,five retrospective studies and three prospective studies were found.Similarly,five retrospective studies and two prospective studies were also included for papers comparing CT to PET scans.Only one retrospective study and one prospective study were found to be suitable for papers comparing CT to magnetic resonance imaging scans.RESULTS Staging laparoscopy outperformed computed tomography in all measured aspects,namely sensitivity,specificity,positive predictive value and negative predictive value.Magnetic resonance imaging and PET produced mixed results,with the former shown to be only marginally better than computed tomography.CT performed slightly better than PET in most measured domains,except in specificity and true negative rates.We speculate that this may be due to the limited F-fluorodeoxyglucose uptake in small peritoneal metastases and in linitis plastica.Radiomic modelling,in its current state,shows promise as an alternative for predicting peritoneal metastases.With further research,deep learning and radiomic modelling can be refined and potentially applied as a preoperative diagnostic tool to reduce the need for invasive staging laparoscopy.CONCLUSION Staging laparoscopy was superior in all measured aspects.However,associated risks and costs must be considered.Refinements in radiomic modelling are necessary to establish it as a reliable screening technique.

Application of CD34 expression combined with three-phase dynamic contrast-enhanced computed tomography scanning in preoperative staging of gastric cancer

BACKGROUND Accurate preoperative staging of gastric cancer(GC),a common malignant tumor worldwide,is critical for appropriate treatment plans and prognosis.Dynamic three-phase enhanced computed tomography(CT)scanning for preoperative staging of GC has limitations in evaluating tumor angiogenesis.CD34,a marker on vascular endothelial cell surfaces,is promising in evaluating tumor angiogenesis.We explored the value of their combination for preoperative staging of GC to improve the efficacy and prognosis of patients with GC.Medical records of 106 patients with GC treated at the First People's Hospital of Lianyungang between February 2021 and January 2023 were retrospectively studied.All patients underwent three-phase dynamic contrast-enhanced CT scanning before surgery,and CD34 was detected in gastroscopic biopsy specimens.Using surgical and pathological results as the gold standard,the diagnostic results of three-phase dynamic contrast-enhanced CT scanning at different T and N stages were analyzed,and the expression of CD34-marked microvessel density(MVD)at different T and N stages was determined.The specificity and sensitivity of three-phase dynamic contrast-enhanced CT and CD34 in T and N staging were calculated;those of the combined diagnosis of the two were evaluated in parallel.Independent factors affecting lymph node metastasis were analyzed using multiple logistic regression.RESULTS The accuracy of three-phase dynamic contrast-enhanced CT scanning in diagnosing stages T1,T2,T3 and T4 were 68.00%,75.00%,79.41%,and 73.68%,respectively,and for diagnosing stages N0,N1,N2,and N3 were 75.68%,74.07%,85.00%,and 77.27%,respectively.CD34-marked MVD expression increased with increasing T and N stages.Specificity and sensitivity of three-phase dynamic contrast-enhanced CT in T staging were 86.79%and 88.68%;for N staging,89.06%and 92.86%;for CD34 in T staging,64.15%and 88.68%;and for CD34 in N staging,84.38%and 78.57%,respectively.Specificity and sensitivity of joint diagnosis in T staging were 55.68%and 98.72%,and N staging were 75.15%and 98.47%,respectively,with the area under the curve for diagnosis improving accordingly.According to multivariate analysis,a longer tumor diameter,higher pathological T stage,lower differ-entiation degree,and higher expression of CD34-marked MVD were independent risk factors for lymph node metastasis in patients with GC.CONCLUSION With high accuracy in preoperatively determining the invasion depth and lymph node metastasis of GC,CD34 expression and three-phase dynamic contrast-enhanced CT can provide a reliable basis for surgical resection.

Progress of Imaging Histology in the Diagnosis and TNM Staging of Gastric Cancer

Gastric cancer is one of the most common malignant tumours with complex dynamic heterogeneity and aggressiveness, and the information that can be evaluated by traditional imaging is limited and subjective. With the development of machine learning, radiomics can combine medical imaging with genomics and proteomics to discover latent information, a feature that makes it a beneficial aid to assist physicians in clinical decision making and is used in all areas of gastric cancer diagnosis and treatment. In this paper, we describe the workflow of radiomics and the research progress in gastric cancer diagnosis.