Clinical significance of lymph node metastasis in gastric cancer

Gastric cancer,one of the most common malignancies in the world,frequently reveals lymph node,peritoneum,and liver metastases.Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection,which results in poor prognosis.Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer.Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials,it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year followup study.Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide,but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis.It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer.Besides,the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer.

Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer

AIM: To investigate the impact of prognostic nutritional index (PNI) on the postoperative complications and long-term outcomes in gastric cancer patients undergoing total gastrectomy.

Characteristics and prognosis of gastric cancer in patients aged ≥ 70 years

AIM:To elucidate the prognostic value of age for gastric cancer and identify the optimal treatment for elderly gastric cancer patients.METHODS:We enrolled 920 patients with gastric cancer who underwent gastrectomy between January 2003and December 2007 in our center.Patients were categorized into three groups:younger group(age<50years),middle-aged group(50-69 years),and elderly group(≥70 years).Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed.The log-rank test was used to assess statistical differences between curves.Independent prognostic factors were identified by the Cox proportional hazards regression model.Stratified analysis was used to investigate the impact of age on survival at each stage.Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer.We analyzed the potential prognostic factors for patients aged≥70years.Finally,the impact of extent of lymphadenectomy and postoperative chemotherapy on survival for each age group was evaluated.RESULTS:In the elderly group,there was a male predominance.At the same time,cancers of the upper third of the stomach,differentiated type,and less-invasive surgery were more common than in the younger or middle-aged groups.Elderly patients were more likely to have advanced tumor-node-metastasis(TNM)stage and larger tumors,but less likely to have distant metastasis.Although 5-year overall survival(OS)rate specific to gastric cancer was not significantly different among the three groups,elderly patients demonstrated a significantly lower 5-year OS rate than the younger and middle-aged patients(elderly vs middle-aged vs younger patients=22.0%vs 36.6%vs 38.0%,respectively).In the TNM-stratified analysis,the differences in OS were only observed in patients withⅡandⅢtumors.In multivariate analysis,only surgical margin status,pT4,lymph node metastasis,M1 and sex were independent prognostic factors for elderly patients.The5-year OS rate did not differ between elderly patients undergoing D1 and D2 lymph node resection,and these patients benefited little from chemotherapy.CONCLUSION:Age≥70 years was an independent prognostic factor for gastric cancer after gastrectomy.D1 resection is appropriate and postoperative chemotherapy is possibly unnecessary for elderly patients with gastric cancer.

Impact of intraoperative blood loss on survival after curative resection for gastric cancer

AIM:To elucidate the potential impact of intraoperative blood loss(IBL)on long-term survival of gastric cancer patients after curative surgery.METHODS:A total of 845 stageⅠ-Ⅲgastric cancer patients who underwent curative gastrectomy between January 2003 and December 2007 in our center were enrolled in this study.Patients were divided into 3groups according to the amount of IBL:group 1(<200mL),group 2(200-400 mL)and group 3(>400 mL).Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed.The Log-rank test was used to assess statistical differences between the groups.Independent prognostic factors were identified by the Cox proportional hazards regression model.Stratified analysis was used to investigate the impact of IBL on survival in each stage.Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer.Finally,we explored the possible factors associated with IBL and identified the independent risk factors for IBL≥200 mL.RESULTS:Overall survival was significantly influenced by the amount of IBL.The 5-year overall survival rates were 51.2%,39.4%and 23.4%for IBL less than 200mL,200 to 400 mL and more than 400 mL,respectively(<200 mL vs 200-400 mL,P<0.001;200-400 mL vs>400 mL,P=0.003).Age,tumor size,Borrmann type,extranodal metastasis,tumour-node-metastasis(TNM)stage,chemotherapy,extent of lymphadenectomy,IBL and postoperative complications were found to be independent prognostic factors in multivariable analysis.Following stratified analysis,patients staged TNMⅠ-Ⅱand those with IBL less than 200 mL tended to have better survival than those with IBL not less than 200mL,while patients staged TNMⅢ,whose IBL was less than 400 mL had better survival.Tumor location,tumor size,TNM stage,type of gastrectomy,combined organ resection,extent of lymphadenectomy and year of surgery were found to be factors associated with the amount of IBL,while tumor location,type of gastrectomy,combined organ resection and year of surgery were independently associated with IBL≥200 mL.CONCLUSION:IBL is an independent prognostic factor for gastric cancer after curative resection.Reducing IBL can improve the long-term outcome of gastric cancer patients following curative gastrectomy.

STAT-3 correlates with lymph node metastasis and cell survival in gastric cancer

AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor of cytokine signaling-1(SOCS-1),survivin and Bcl-2 in gastric cancer patients after gastrectomy by immunohistochemical method.In addition,in situ hybridization was used to further demonstrate the mRNA expression of STAT3 in gastric cancer.RESULTS:With the univariate analysis,expressions of STAT3,pSTAT3,SOCS-1,survivin and Bcl-2,the size of primary tumor and the lymph node metastasis were found to be associated with the overall survival(OS) of gastric cancer patients.However,only pSTAT3 expression and the lymph node metastasis were identified as the independent factors of OS of gastric cancer with multivariate analysis.STAT3 expression was correlated with the lymph node metastasis.There were positive correlations between expressions of STAT3,survivin,Bcl-2 and pSTAT3 in gastric cancer,whereas there was negative correlation between STAT3 expression and SOCS-1 expression in gastric cancer.CONCLUSION:STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells.SOCS-1 might be the valid molecular antagonist to inhibit the STAT3 expression in gastric cancer.

Selective tropism of liver stem cells to hepatocellular carcinoma in vivo

AIM： To investigate the selective tropism of liver stem cells to hepatocellular carcinoma （HCC） in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS： WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein （EGFP）. An animal model of HCC in Wistar rats was established by implanting HCC cells （CBRH7919） combined with an immunosuppressive drug. EGFP labeled liver stern cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stern cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stern cells within the tumor tissue were observed and analyzed.RESULTS： Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION： Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.

Prognostic value of number of examined lymph nodes in patients with node-negative gastric cancer

AIM: To elucidate the potential impact of examined lymph nodes (eLNs) on long-term survival of node-negative gastric cancer patients after curative surgery.

Analysis of risk factors for the interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy

AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.

Effect of complication grade on survival following curative gastrectomy for carcinoma

AIM: To elucidate the potential impact of the grade of complications on long-term survival of gastric cancer patients after curative surgery.

Bronchogenic cyst of the stomach:A case report

BACKGROUND Gastric bronchogenic cysts(BCs)are extremely rare cystic masses caused by abnormal development of the respiratory system during the embryonic period.Gastric bronchial cysts are rare lesions first reported in 1956;as of 2019,only 37 cases are available in the MEDLINE/PubMed online databases.BCs usually have no clinical symptoms in the early stage,and their imaging findings also lack specificity.Therefore,they are difficult to diagnose before histopathological examination.CASE SUMMARY A 55-year-old woman presented at our hospital with intermittent epigastric pain.She had a slightly high level of serum carbohydrate antigen 72-4(CA 72-4).Endoscopic ultrasound found that a cystic mass originated from the submucosa of the posterior gastric wall near the cardia,indicating a diagnosis of cystic hygroma of the stomach.Furthermore,a computed tomography scan demonstrated a quasi-circular cystic mass closely related to the lesser curvature of the gastric fundus with a low density.Because the imaging examinations did not suggest a malignancy and the patient required complete resection,she underwent laparoscopic surgery.As an intraoperative finding,this cystic lesion was located in the posterior wall of the fundus and contained some yellow viscous liquid.Finally,the pathologists verified that the cyst in the fundus was a gastric BC.The patient recovered well with normal CA 72-4 levels,and her course was uneventful at 10 mo.CONCLUSION This is a valuable report as it describes an extremely rare case of gastric BC.Moreover,this is the first case of BC to present with elevated CA 72-4 levels.

Role of E3 ubiquitin ligases in gastric cancer

E3 ubiquitin ligases have an important role in carcinogenesis and include a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.So far,E3 ubiquitin ligases have been reported to have a role in a variety of biological processes including cell cycle regulation,cell proliferation,and apoptosis.Recently,several kinds of E3 ubiquitin ligases were demonstrated to be generally highly expressed in gastric cancer(GC) tissues and to contribute to carcinogenesis.In this review,we summarize thecurrent knowledge and information about the clinical significance of E3 ubiquitin ligases in GC.Bortezomib,a proteasome inhibitor,encouraged the evaluation of other components of the ubiquitin proteasome system for pharmaceutical intervention.The clinical value of novel treatment strategies targeting aberrant E3 ubiquitin ligases for GC are discussed in the review.

Standardizing the classification of gastric cancer patients with limited and adequate number of retrieved lymph nodes:an externally validated approach using real-world data

Background:Currently,there is no formal consensus regarding a standard classification for gastric cancer(GC)patients with<16 retrieved lymph nodes(rLNs).Here,this study aimed to validate a practical lymph node(LN)staging strategy to homogenize the nodal classification of GC cohorts comprising of both<16(Limited set)and≥16(Adequate set)rLNs.Methods:All patients in this study underwent R0 gastrectomy.The overall survival(OS)difference between the Limited and Adequate set from a large Chinese multicenter dataset was analyzed.Using the 8th American Joint Committee on Cancer(AJCC)pathological nodal classification(pN)for GC as base,a modified nodal classification(N’)resembling similar analogy as the 8th AJCC pN classification was developed.The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance,Epidemiology,and End Results(SEER)dataset comprising of 10,208 multi-ethnic GC cases.Results:Significant difference in OS between the Limited and Adequate set(corresponding N0–N3a)using the 8th AJCC system was observed but the OS of N0_(limited)vs.N1_(adequate),N1_(limited)vs.N2_(adequate),N2_(limited)vs.N3_(aadequate),and N3_(alimited)vs.N3_(badequate)subgroups was almost similar in the Chinese dataset.Therefore,we formulated an N’classification whereby only the nodal subgroups of the Limited set,except for pT1N0M0 cases as they underwent less extensive surgeries(D1 or D1+gastrectomy),were re-classified to one higher nodal subgroup,while those of the Adequate set remained unchanged(N’0=N0_(adequate)+pT1N0M0_(limited),N’1=N1_(adequate)+N0_(limited)(excluding pT1N0M0_(limited)),N’2=N2_(adequate)+N1_(limited),N’3a=N3_(aadequate)+N2_(limited),and N’3b=N3_(badequate)+N3_(alimited)).This N’classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups.Further analyses demonstrated superior statistical performance of the pTN’M system over the 8th AJCC edition and was successfully validated using the SEER dataset.Conclusion:The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with<16 and≥16 rLNs.

Advances in para-aortic nodal dissection in gastric cancer surgery: A review of research progress over the last decade

Approximately 17%-40%of para-aortic lymph node(PAN)metastasis occurs in patients with advanced gastric cancer.As the third tier of lymphatic drainage of the stomach and the final station in front of the systemic circulation,PAN infiltration is defined as distant metastasis and plays a key role in the evaluation of the prognosis of advanced gastric cancer.Many clinical factors including tumor size≥5 cm,pT3 or pT4 depth of tumor invasion,pN2 and pN3 stages,the macroscopic type of Borrmann Ⅲ/Ⅳ,and the diffuse/mixed Lauren classification are indicators of PAN metastasis.Whether PAN dissection(PAND)should be performed on patients with or without the macroscopic PAN invasion remains unascertained,regardless of the numerous retrospective comparative studies reported on the improved prognosis over D2 alone.Another paradoxical result from many other studies showed no significant difference in the overall survival between these two lymphadenectomies.A phase Ⅱ trial launched by the Japan Clinical Oncology Group indicated that two or three courses of S-1 and cisplatin preoperatively followed by radical surgery with D2+PAND and postoperative S-1 is the current standard strategy for the treatment of patients with extensive lymph node metastasis,and this regimen could be substituted by a promising strategy with effective combination chemotherapy or suitable chemotherapy duration.This review focuses on the advances in radical gastrectomy plus PAND with or without chemotherapy for patients with advanced gastric cancer.

一项优化AJCC/UICC pTNM胃癌分期预后预测效能的多中心研究

背景与目的美国癌症联合会与国际抗癌联盟(AmericanJointCommitteeonCancer/UnionforInternationalCancerControl,A JCC/UICC)联合发布的第8版TNM病理分期(pathological tumor?node?metastasis,p TNM)较前进行了重要修改,以提高胃癌患者预后预测准确性。然而,该分期不同亚组间患者的预后仍存在一定的同质性。本研究旨在对比第8版和第7版AJCC/UICC pTNM分期对胃癌预后的预测效能,并纳入外部验证对现有分期进行优化。方法共纳入分析7911例就诊于中国3家大型医疗中心和10,208例美国流行病监测与最终治疗结果(Surveillance Epidemiology and End Results,SEER)数据库的患者临床资料。采用log-rank检验、线性趋势检验、似然比检验和赤池信息量准则(akaike information criterion,AIC)梯度评估第7、8版AJCC/UICC pTNM分期系统的同质性、辨别力和单调性,在此基础上优化分期并以SEER数据集作为外部验证。结果第7、8版分期系统在两组数据集中均存在明显分期偏移,且集中在III期患者。IIIA、IIIB和IIIC期各亚组内患者的生存率有显著差异,表明两个系统分期分层的同质性较差。我们根据中国患者数据构建一个新的改良版p TNM分期,上述分层同质性问题得到明显改善,进一步以SEER数据作为验证集同样得到了良好的结果。相较第7、8版分期系统,改良版p TNM分期在两组数据集中均有较高的log-rank、线性趋势、似然比卡方值和较低的AIC值,显示出更优的辨别力、同质性、单调性和预后预测效能。结论第8版AJCC/UICC pTNM分期系统优于第7版,但预后预测的同质性均较差。我们构建的改良版p TNM分期在两组大样本胃癌数据集中均显示出理想的分期分层和预后预测效能。

Adenocarcinoma of esophagogastric junction

To date,there has been a dramatic increase in the incidence of adenocarcinomas of the esophagogastric junction （AEG）worldwide.The classification of AEG,defined by Siewert and Stein,was approved at the second International Gastric Cancer Congress in Munich in April 1997.In accordance with the anatomic cardia,EGJC can be divided into three subtypes：type Ⅰ,adenocarcinoma of the distal esophagus with the center located within 1 cm above and 5 cm above the anatomic esophagogastric junction （EGJ）;type Ⅱ,true carcinoma of the cardia with the tumor center within 1 cm above and 2 cm below the EGJ;type Ⅲ,subcardial carcinoma with the tumor center between 2 and 5 cm below EGJ,which infiltrates the EGJ and distal esophagus from below （1）.

Effects of extended lymphadenectomy and postoperative chemotherapy on node-negative gastric cancer

AIM:To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis.METHODS:Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected,from January 2002 to December 2006,were analyzed retrospectively.Patients with pT4 stage or distant metastasis were excluded.We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features,such as age,tumor size,tumor location and depth of invasion.At the same time,the relationship between postoperative chemotherapy and the5-year survival rate among different subgroups were also analyzed.RESULTS:The overall 5-year survival rate of the entire cohort was 63.7%.The 5-year survival rate was poor in those patients who were:(1)more than 65 years old;(2)with tumor size larger than 4 cm;(3)with tumor located in the upper portion of the stomach;and(4)with pT3 tumor.The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor(P=0.019),but not in other subgroups.Moreover,there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups(P>0.05).CONCLUSION:For gastric cancer patients without lymph node metastasis,extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor.However,there was no evidence of a survival benefit from postoperative chemotherapy alone.

Risk of station 12a lymph node metastasis in patients with lowerthird gastric cancer

BACKGROUND Controversy over the issue that No.12a lymph node involvement is distant or regional metastasis remains,and the possible inclusion of 12a lymph nodes in D2 lymphadenectomy is unclear.As reported,gastric cancer(GC)located in the lower third is highly related to the metastasis of station 12a lymph nodes.AIM To investigate whether the clinicopathological factors and metastasis status of other perigastric nodes can predict station 12a lymph node metastasis and evaluate the prognostic significance of station 12a lymph node dissection in patients with lower-third GC.METHODS A total of 147 patients with lower-third GC who underwent D2 or D2+lymphadenectomy,including station 12a lymph node dissection,were included in this retrospective study from June 2003 to March 2011.Survival prognoses were compared between patients with or without station 12a lymph node metastasis.Logistic regression analyses were used to clarify the association between station 12a lymph node metastasis and clinicopathological factors or metastasis status of other perigastric nodes.The metastasis status of each regional lymph node was evaluated to identify the possible predictors of station 12a lymph node metastasis.RESULTS Metastasis to station 12a lymph nodes was observed in 18 patients with lowerthird GC,but not in 129 patients.The incidence of station 12a lymph node involvement was reported as 12.2%in patients with lower-third GC.The overall survival of patients without station 12a lymph node metastasis was significantly better than that of patients with station 12a metastasis(P<0.001),which could also be seen in patients with or without extranodal soft tissue invasion.Station 12a lymph node metastasis and extranodal soft tissue invasion were identified as independent predictors of poor prognosis in patients with lower-third GC.Advanced pN stage was defined as independent risk factor significantly correlated with station 12a lymph node positivity.Station 3 lymph node staus was also proven to be significantly correlated with station 12a lymph node involvement.CONCLUSION Metastasis of station 12a lymph nodes could be considered an independent prognosis factor for patients with lower-third GC.The dissection of station 12a lymph nodes may not be ignored in D2 or D2+lymphadenectomy due to difficulties in predicting station 12a lymph node metastasis.

Examined lymph node count for gastric cancer patients after curative surgery

Lymph node(LN)metastasis is the most common form of metastasis in gastric cancer(GC).The status and stage of LN metastasis are important indicators that reflect the progress of GC.The number of LN metastases is still the most effective index to evaluate the prognosis of patients in all stages of LN metastasis.Examined LN(ELN)count refers to the number of LNs harvested from specimens by curative gastrectomy for pathological examination.This review summarizes the factors that influence ELN count,including individual and tumor factors,intraoperative dissection factors,postoperative sorting factors,and pathological examination factors.Different ELN counts will lead to prognosis-related stage migration.Fine LN sorting and regional LN sorting are the two most important LN sorting technologies.The most direct and effective way to harvest a large number of LNs is for surgeons to perform in vitro fine LN sorting.

新型列线图用于进展期胃癌D2根治术后的个体化预后预测

背景与目的目前鲜有文献报道接受D2根治性切除术的进展期胃癌(advanced gastric cancer,AGC)患者的疾病特异性生存(disease?specific survival,DSS)预测系统,尤其针对中国胃癌患者。本研究拟构建一种精准预测中国进展期胃癌患者预后的列线图(Nomogram)模型。方法回顾性纳入2000年1月1日至2012年12月31日间在中国三家大型医院接受D2胃切除术的6753例AGC患者。中山大学肿瘤防治中心患者作为训练集,中国医科大学附属第一医院和天津医科大学肿瘤医院患者作为两个独立的外部验证集。在训练集中采用Cox比例风险回归模型进行多因素生存分析,并构建Nomogram模型,在验证集中通过Harrell’s C-index和校准曲线评价该模型的准确性、实际生存情况和模型预测的一致性。结果 Cox回归模型显示年龄、肿瘤大小、部位、Lauren分型、淋巴管/血管浸润、肿瘤浸润深度和淋巴结转移率为患者预后相关因素。在训练集中,Nomogram模型的预测准确度较美国癌症研究联合会(American Joint Committee on Cancer,AJCC)TNM癌症分期系统(第8版)更高(C-index,0.82 vs. 0.74,P <0.001)。在两个验证集中,亦出现类似的结果(C-index分别为0.83 vs. 0.75和0.81 vs. 0.74;两者均P <0.001)。校准曲线显示Nomogram模型预测的患者生存与和实际生存高度接近。结论本研究构建的Nomogram模型能够预测AGC患者的3年、 5年和10年疾病特异性生存,经外部验证显示其具有较高的准确性和区分效能,预示潜在的临床应用前景。

Proposal and validation of a modified staging system to improve the prognosis predictive performance of the 8th AJCC/ UICC pTNM staging system for gastric adenocarcinoma: a multicenter study with external validation

Background:The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control(AJCC/UICC)pathological tumor-node-metastasis(pTNM)staging system may have increased accuracy in predicting prognosis of gastric cancer due to its important modifications from previous editions.However,the homogeneity in prognosis within each subgroup classified according to the 8th edition may still exist.This study aimed to compare and analyze the prognosis prediction abilities of the 8th and 7th editions of AJCC/UICC pTNM staging system for gastric cancer and propose a modified pTNM staging system with external validation.Methods:In total,clinical data of 7911 patients from three high-capacity institutions in China and 10,208 cases from the Surveillance,Epidemiology,and End Results(SEER)Program Registry were analyzed.The homogeneity,discrimina-tory ability,and monotonicity of the gradient assessments of the 8th and 7th editions of AJCC/UICC pTNM staging system were compared using log-rank χ^(2),linear-trend χ^(2),likelihood-ratioχ2 statistics and Akaike information criterion(AIC)calculations,on which a modified pTNM classification with external validation using the SEER database was proposed.Results:Considerable stage migration,mainly for stage III,between the 8th and 7th editions was observed in both cohorts.The survival rates of subgroups of patients within stage IIIA,IIIB,or IIIC classified according to both editions were significantly different,demonstrating poor homogeneity for patient stratification.A modified pTNM staging system using data from the Chinese cohort was then formulated and demonstrated an improved homogeneity in these abovementioned subgroups.This staging system was further validated using data from the SEER cohort,and similar promising results were obtained.Compared with the 8th and 7th editions,the modified pTNM staging system displayed the highest log-rank χ^(2),linear-trend χ^(2),likelihood-ratio χ^(2),and lowest AIC values,indicating its superior discriminatory ability,monotonicity,homogeneity and prognosis prediction ability in both populations.Conclusions:The 8th edition of AJCC/UICC pTNM staging system is superior to the 7th edition,but still results in homogeneity in prognosis prediction.Our modified pTNM staging system demonstrated the optimal stratification and prognosis prediction ability in two large cohorts of different gastric cancer populations.