| Objective: To analyse the clinicopathological characteristics and thepattern of metastatic lymph node dissemination and prognostic factors inpatients after radical resection with adenocarcinoma of the esophagogastricjunction (AEG), in order to offer a theoretical reference for adjuvant therapyto the clinical practice.Methods: A total of393AEG patients undergone radical resection withexamined lymph nodes≥8were selected in the fourth hospital of Hebeimedical university from January2006to January2009.According to Siewertclassification, there were26patients with adenocarcinoma of the distalesophagus (Type I),139patients with true carcinoma of cardia (Type II), and228patients with subcardial carcinoma (Type III). The distribution of thecancer TNM stage showed4cases for StageⅠA,24cases for StageⅠB,8casesfor StageⅡA,94cases for StageⅡB,64cases for StageⅢA,97cases for StageⅢB,102cases for Stage ⅢC. A total of5119lymph node were removed with1492positive lymph nodes.149cases undergone adjuvant chemotherapy, withthe median chemotherapy cycles of3(1~9). The effect of gender, age, SiewertSubtypes,tumor maximum diameter, tumor differentiation degree,Lymphovascular invasion, pathological type, depth of tumor invasion, thenumber of cleaned lymph node, whether lymph node metastasis, lymph nodemetastasis ratio, N stage, negative lymph node number, adjuvantchemotherapy on survival were analyzed. The pattern of recurrence was alsoanalyzed, Adjunctive treatment strategy and postoperative chemotherapybenefit people were explored.Results:1clinicopathological characteristics (1)Lymph node metastasis rate was70.0%(275of393patients)and lymphnodes metastatic ratio(LNR)was29.1%(1492/5119);The abdominal lymphnodes metastasis rate and LNR was69.2%(272/393) and31.3%(1452/4637);The mediastinum lymph node metastasis rate and LNR was16.4%(24/146)and8.3%(40/481).(2) Mediastinal lymph node metastasis occurred mainly in the loweresophagus and carina.The abdominal sites with the highest number of positiveLNs were the paracardiac, lesser curvature, left gastric artery, celiacartery,splenic hilum and the splenic artery.(3)All Siewert subtypes had a higher lymph node metastatic rate and ratioin abdominal than mediastinum (χ2=13.487, P=0.000; χ2=52.775, P=0.000;χ2=53.214, P=0.000; χ2=3.223, P=0.073; χ2=59.900, P=0.000; χ2=34.107,P=0.000). Compared with Type I, Type II and Type III had a lowermediastinum lymphatic metastasis rate(χ2=11.963, P=0.003), while abdominallymph node metastasis ratio was higher(χ2=12.998, P=0.002);(4) Tumor maximum diameter≥4cm had a higher lymph node metastasisrate and LNR than those if tumor maximum diameter＜4cm (χ2=13.636,P=0.000; χ2=64.767, P=0.000);(5) With enhancement of tumor invasion, lymphatic metastasis and ratiowere both increased (χ2=35.305, P=0.000; χ2=134.034, P=0.000);(6) Poor-differentiated adenocarcinoma was more frequent lymph nodemetastasis rates and LNR than well-differentiated andmorderate (χ2=14.468,P=0.000; χ2=120.099, P=0.000);(7) Lymphovascular invasion had high rate of lymph node metastasis andLNR (χ2=7.946，P=0.005；χ2=112.723，P=0.000);(8) Mucinous and signet ring cell adenocarcinoma had high rate of lymphnode metastasis and LNR than adenocarcinoma(χ2=8.710, P=0.000; χ2=2.714,P=0.099).2Univariate and multivariate analysis of influence on lymphatic metastasisand the depth of tumor invasion(1)Univariate analysis showed that depth of tumor invasion had correlation with maximum diameter and differentiation (P<0.05), tumormaximum diameter was an independent factor for depth of tumor invasion(P=0.013);(2)Lymphatic metastasis had relation to tumor maximum diameter,lymphovascular invasion and differentiation (P<0.05); Logistic multivariateanalysis showed lymphovascular invasion was an independent predictor forlymphatic metastasis(P=0.002).3SurvivalA total of245patients died,1-,3-,5-year overall survival rates were81.7%,50.9%and38.7%respectively.3.1Clinicopathological factors and survivalThe1-,3-,5-year overall survival rates in patients received thoracicapproach operation showed no significant difference with those receivedabdominal approach (χ2=0.572, P=0.450). Prognosis of Siewert typy II wasthe best, followed by typy III, and typy I was the worst (χ2=7.186, P=0.028).The1-,3-,5-year overall survival rates in patients with adenocarcinoma weresignificantly better than those with mucinous adenocarcinoma and signet ringcell carcinoma (χ2=5.329, P=0.021). The1-,3-,5-year overall survival rates intumor maximal diameter≥4cm group were80.1%,48.8%,36.1%, lower than93.6%,66.0%,57.4%in <4cm (χ2=8.694, P=0.003), The1-,3-,5-year overallsurvival rates in patients with poor differentiation, lymphovascular invasionwere lower than those with high differentiation, without lymphovascularinvasion (χ2=5.244, P=0.022; χ2=6.622, P=0.010).With enhancement of tumorinvasion depth,1-,3-,5-year overall survival rates decreased (χ2=32.974,P=0.000). The1-,3-,5-year overall survival rates in patients with lymphaticmetastasis were lower than those without lymphatic metastasis (χ2=43.206,P=0.000), and they decreased gradually with the number of lymphaticmetastasis increased (χ2=90.155, P=0.000). According to negative lymphnumber, patients were divided into three groups:＞15，≤15and>9and≤9,1-,3-,5-year overall survival rates in these three groups decreased with reductionof negative lymph number (χ2=7.455, P=0.024). Lymphatic ratio was divided into0%,≤50%and>50%,1-,3-,5-year overall survival rates in these threegroups decreased with increasement of lymphatic ratio(χ2=94.281, P=0.000).4Therapy pattern(1)A total of149cases of patients with postoperative adjuvantchemotherapy, adjuvant chemotherapy group had a higher1-,3-, and5-yearsurvival rates (87.9%,54.4%,44.5%) than those in surgery group (77.9%,48.8%,35.2%)(χ2=3.930, P=0.047).(2)adjuvant chemotherapy cycles≥6had a higher1-,3-, and5-yearsurvival rates (97.2%,66.7%,57.7%) than those whose cycles<6(85.0%,50.4%,40.3%)(χ2=4.060, P=0.044).(3)FLP chemotherapy regimen and FOLFOX chemotherapy regimen hada similar survival rates(χ2=2.016, P=0.156).(4)Stratified analysis showed: postoperative adjuvant chemotherapy hadno significant difference with survival in patients with no lymphatic metastasis,lymphatic ratio≤50%, T1~2and moderate-well differentiated carcinoma(χ2=1.650, P=0.199; χ2=1.241, P=0.265; χ2=0.102, P=0.750; χ2=0.420,P=0.517). The1-,3-,5-year overall survival rates in patients with lymphaticmetastasis, lymphatic ratio≥50%, T3~4and poor differentiated carcinomareceived postoperative adjuvant chemotherapy were higher than thosereceived operation only (χ2=4.081, P=0.03; χ2=6.794, P=0.000; χ2=7.192,P=0.007; χ2=4.836, P=0.028).5Prognostic analysis(1)By univariate analysis, Siewert subtypes, histology type, tumormaximum diameter, differentiation, lymphovascular invasion, T stage, N stage,Negative lymph node number, LRN, adjuvant therapy were main predictorsfor overall survival (P＜0.05);(2) By Cox multivariate analysis, depth oftumor invasion, LNR and adjuvant chemotherapy were independent predictorsfor overall survival(P＜0.05).6Analysis of recurrenceA total of92cases could be followed to recurrence and metastasis. Theaverage time to recurrence was17.3士1.8months, median was12months; Recurrence sits were abdominal lymph node61.8%(34/55), anastomosis38.2%(21/55), mediastinal lymph node12.7%(7/55), gastric stump3.6%(2/55);Visceral metastasis was30.4%(28/92), including hepatic metastasis28.3%(26/92), followed by adrenal3.3%(3/92); Peritoneal metastasis rate was29.3%(27/92), wherein the supraclavicular lymph node in10.9%(10/92), lungin9.8%(9/92), brain in6.5%(6/92), bone5.4%(5/92); Peritoneal implantationrate was6.5%(6/92).6.1Comparison of lymph node metastasis rates in recurrence patients andoverall patientsLymphatic metastasis rates in recurrence patients and overall patientswere88.0%and70.0%, LNR were39.0%and29.1%;The recurrence patientswith a higher Lymph node metastasis rates and LNR than overall patients(χ2=12.467, P=0.000; χ2=45.667, P=0.000).6.2Distribution of abdominal and mediastinal lymphatic metastasis in patientswith postoperative recurrence(1)Abdominal lymphatic metastasis rate in recurrence patients andoverall abdominal patients were88.0%and69.0%and LNR were44.6%and31.3%, there was significant difference (χ2=13.347, P=0.000; χ2=66.886,P=0.000).(2)Mediastinal lymphatic metastasis rate in recurrence patients andoverall mediastinal patients were14.3%and10.0%and LNR were16.4%and8.3%, but there was no significant difference (χ2=0.097, P=0.760; χ2=0.336,P=0.562). It showed that the lymphatic metastasis rates in the paracardial (theleft and right) region and the left gastric artery were both higher (P＜0.05), theparacardial (the left and right) region, the lesser curvature, and the left gastricartery, pyloric, and hepatic artery as the predominating areas of lymph nodemetastases(P＜0.05), followed by the lower paraesophageal (P＞0.05).Conclusions:1AEG has a high rate of lymphatic metastasis, its rate and ration inabdomen are both higher than those in mediastinum; High-risk lymphaticareas of abdomen include paracardial (the left and right) region, lesser curvature, left gastric artery, hepatic artery, splenic portal and splenic arterysurrounding. High-risk lymphatic areas of mediastinum includes the loweresophagus and subcarinal;Lymphatic metastasis rate in mediastinum ofSiewert I is higher than those of Siewert II and Siewert III, metastasis ratio inabdomen of Siewert I is lower than those of Siewert II and Siewert III. Theimportant radiation areas of lymphatic drainage are lower esophagus, stomach,hepatic artery and celiac lymph node region. Siewert I should include middlemediastinal lymphatic drainage area, Siewert II and III should include spleenhilum and splenic artery lymphatic drainage area, But the stomach big curvedon’t have to be taken into consideration; Patients with higher lymph nodemetastasis ratio more should be the priority groups for radiotherapy.2Local recurrence is common seen in anastomotic stoma, abdominalmetastasis, it is recommended to attach importance to these high-risk ofrecurrence.3Tumor maximum diameter is an independent factor for T stage;lymphovascular invasion is an independent factor for lymphatic metastasis.4Survival rate in patients received transthoracic operation approach hasno significant difference with that received transabdomen.5Depth of tumor invasion, lymphatic metastasis ratio and adjuvantchemotherapy are independent factors for survival.6The survival rate in patients received adjuvant chemotherapy issuperior to that received operation only, and benefit patients are withlymphatic metastasis, ratio>50%, T3~4and poor differentiated, therefore it issuggested to received postoperative chemotherapy.7Cycle≥6group has obvious survival advantage to that cycle <6.8Regarding survival rate, there is no significant difference betweenFOLFOX and FLP. |
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