目的 探讨肝细胞癌(以下简称肝癌)大体形态分型与患者临床病理特征及预后的关系,以及影响肝癌患者预后的相关因素.方法 回顾性分析2008年1月至2013年12月南京大学医学院附属鼓楼医院收治的119例肝癌患者的临床资料.将手术切除标本沿冠状位切成厚度约1 cm的切片并拍照,记录病理学特点.参照文献,结合临床经验,将肝癌手术切除标本大体形态分为结节型(1型)、结节突起型(2型)、结节融合型(3型)、浸润型(4型).比较4种类型患者的临床病理因素.采用门诊及电话方式进行随访,随访时间截至2014年4月或患者死亡.正态分布的计量资料以x±s表示,多组间比较采用方差分析,两两比较采用LSD-t检验;偏态分布数据以M(P25,P75)表示,多组间比较采用Kruskal-Wallis检验,两两比较采用Mann-Whitney检验.计数资料比较和单因素分析采用x2检验或Fisher确切概率法.采用Kaplan-Meier法绘制生存曲线,Log-rank检验进行生存分析.采用COX逐步回归模型进行多因素分析.结果 119例肝癌患者中,1型占20.17％ (24/119),2型占25.21％ (30/119),3型占21.85％(26/119),4型占32.77％(39/119).4种不同大体形态分型的肝癌患者年龄、HBsAg阳性、术前AFP、手术时间、术中出血量、住院时间、T分期、微血管侵犯比较,差异均有统计学意义(F =4.499,x2=2.944,3.516,F=1.028,2.837,2.419,x2=6.606,12.732,P＜0.05).进一步两两比较:患者术前AFP,4型显著高于3型、2型和1型,差异均有统计学意义(Z=2.183,1.851,2.083,P＜0.05).患者手术时间,4型显著长于3型和1型,差异均有统计学意义(t=1.825,1.758,P＜0.05);4型与2型比较,差异无统计学意义(t=1.521,P＞0.05).患者术中出血量,4型显著多于3型、2型和1型,差异均有统计学意义(t=1.769,1.875,2.205,P＜0.05).患者住院时间,4型显著长于2型和1型,差异均有统计学意义(t=2.159,1.975,P＜0.05);4型与3型比较,差异无统计学意义(t=0.248,P＞0.05).患者微血管侵犯,4型显著多于3型、2型和1型,差异均有统计学意义(x2=5.905,8.291,4.729,P＜0.05).119例肝癌患者中,116例术后获得随访,随访率为97.48％(116/119),中位随访时间为26个月(4～74月).119例患者总体中位生存时间为25个月(1～73个月),1、3、5年总体生存率分别为83.2％、70.7％、63.4％;无瘤中位生存时间为14个月(1～70个月),1、3、5年无瘤生存率分别为73.3％、42.7％、11.4％.1型肝癌患者总体中位生存时间为56个月(51 ～61个月),1、3、5年总体生存率分别为94.1％、82.5％、65.3％,无瘤中位生存时间为48个月(41 ～54个月),1、3、5年无瘤生存率分别为81.3％、66.7％、58.6％;2型肝癌患者总体中位生存时间为56个月(52 ～ 60个月),1、3、5年总体生存率分别为91.6％、82.6％、82.6％,无瘤中位生存时间为46个月(40～51个月),1、3、5年无瘤生存率分别为81.4％、64.1％、64.1％;3型肝癌患者总体中位生存时间为53个月(48 ～58个月),1、3、5年总体生存率分别为91.6％,84.7％,77.8％,无瘤中位生存时间为42个月(36 ～48个月),1、3、5年无瘤生存率分别为80.1％、62.3％、50.0％;4型肝癌患者总体中位生存时间为46个月(40 ～51个月),1、3、5年总体生存率分别为65.7％、51.5％、45.6％,无瘤中位生存时间为29个月(23 ～34个月),1、3、5年无瘤生存率分别为64.3％、31.6％、22.3％.不同大体形态分型肝癌患者预后(总体生存率和无瘤生存率)比较,差异有统计学意义(x2=7.971,7.652,P＜0.05).患者预后(总体生存率和无瘤生存率)4型显著差于3型、2型和1型,差异均有统计学意义(总体生存率:x2=4.823,6.131,5.785,P＜0.05;无瘤生存率:x2=5.184,5.634,9.262,P＜0.05).单因素分析结果显示:术前AFP、T分期、微血管侵犯、肿瘤大体形态分型是影响肝癌患者预后的相关因素(x2=3.516,6.687,6.165,7.974,P＜0.05).多因素分析结果显示:T3 ～T4期、微血管侵犯、肿瘤大体形态分型为4型是影响肝癌患者预后的独立危险因素(RR=3.646,2.397,1.617,95％可信区间:1.042 ～ 12.713,1.063 ～5.403,1.119 ～2.337,P＜0.05).结论 肝癌的大体形态分型可能与患者临床病理因素相关,浸润型肝癌患者术前AFP高、术中出血量大、微血管侵犯发生率高,预后差.T3～T4期、微血管侵犯、肿瘤大体形态分型为浸润型是影响肝癌患者预后的独立危险因素.
目的 探討肝細胞癌(以下簡稱肝癌)大體形態分型與患者臨床病理特徵及預後的關繫,以及影響肝癌患者預後的相關因素.方法 迴顧性分析2008年1月至2013年12月南京大學醫學院附屬鼓樓醫院收治的119例肝癌患者的臨床資料.將手術切除標本沿冠狀位切成厚度約1 cm的切片併拍照,記錄病理學特點.參照文獻,結閤臨床經驗,將肝癌手術切除標本大體形態分為結節型(1型)、結節突起型(2型)、結節融閤型(3型)、浸潤型(4型).比較4種類型患者的臨床病理因素.採用門診及電話方式進行隨訪,隨訪時間截至2014年4月或患者死亡.正態分佈的計量資料以x±s錶示,多組間比較採用方差分析,兩兩比較採用LSD-t檢驗;偏態分佈數據以M(P25,P75)錶示,多組間比較採用Kruskal-Wallis檢驗,兩兩比較採用Mann-Whitney檢驗.計數資料比較和單因素分析採用x2檢驗或Fisher確切概率法.採用Kaplan-Meier法繪製生存麯線,Log-rank檢驗進行生存分析.採用COX逐步迴歸模型進行多因素分析.結果 119例肝癌患者中,1型佔20.17％ (24/119),2型佔25.21％ (30/119),3型佔21.85％(26/119),4型佔32.77％(39/119).4種不同大體形態分型的肝癌患者年齡、HBsAg暘性、術前AFP、手術時間、術中齣血量、住院時間、T分期、微血管侵犯比較,差異均有統計學意義(F =4.499,x2=2.944,3.516,F=1.028,2.837,2.419,x2=6.606,12.732,P＜0.05).進一步兩兩比較:患者術前AFP,4型顯著高于3型、2型和1型,差異均有統計學意義(Z=2.183,1.851,2.083,P＜0.05).患者手術時間,4型顯著長于3型和1型,差異均有統計學意義(t=1.825,1.758,P＜0.05);4型與2型比較,差異無統計學意義(t=1.521,P＞0.05).患者術中齣血量,4型顯著多于3型、2型和1型,差異均有統計學意義(t=1.769,1.875,2.205,P＜0.05).患者住院時間,4型顯著長于2型和1型,差異均有統計學意義(t=2.159,1.975,P＜0.05);4型與3型比較,差異無統計學意義(t=0.248,P＞0.05).患者微血管侵犯,4型顯著多于3型、2型和1型,差異均有統計學意義(x2=5.905,8.291,4.729,P＜0.05).119例肝癌患者中,116例術後穫得隨訪,隨訪率為97.48％(116/119),中位隨訪時間為26箇月(4～74月).119例患者總體中位生存時間為25箇月(1～73箇月),1、3、5年總體生存率分彆為83.2％、70.7％、63.4％;無瘤中位生存時間為14箇月(1～70箇月),1、3、5年無瘤生存率分彆為73.3％、42.7％、11.4％.1型肝癌患者總體中位生存時間為56箇月(51 ～61箇月),1、3、5年總體生存率分彆為94.1％、82.5％、65.3％,無瘤中位生存時間為48箇月(41 ～54箇月),1、3、5年無瘤生存率分彆為81.3％、66.7％、58.6％;2型肝癌患者總體中位生存時間為56箇月(52 ～ 60箇月),1、3、5年總體生存率分彆為91.6％、82.6％、82.6％,無瘤中位生存時間為46箇月(40～51箇月),1、3、5年無瘤生存率分彆為81.4％、64.1％、64.1％;3型肝癌患者總體中位生存時間為53箇月(48 ～58箇月),1、3、5年總體生存率分彆為91.6％,84.7％,77.8％,無瘤中位生存時間為42箇月(36 ～48箇月),1、3、5年無瘤生存率分彆為80.1％、62.3％、50.0％;4型肝癌患者總體中位生存時間為46箇月(40 ～51箇月),1、3、5年總體生存率分彆為65.7％、51.5％、45.6％,無瘤中位生存時間為29箇月(23 ～34箇月),1、3、5年無瘤生存率分彆為64.3％、31.6％、22.3％.不同大體形態分型肝癌患者預後(總體生存率和無瘤生存率)比較,差異有統計學意義(x2=7.971,7.652,P＜0.05).患者預後(總體生存率和無瘤生存率)4型顯著差于3型、2型和1型,差異均有統計學意義(總體生存率:x2=4.823,6.131,5.785,P＜0.05;無瘤生存率:x2=5.184,5.634,9.262,P＜0.05).單因素分析結果顯示:術前AFP、T分期、微血管侵犯、腫瘤大體形態分型是影響肝癌患者預後的相關因素(x2=3.516,6.687,6.165,7.974,P＜0.05).多因素分析結果顯示:T3 ～T4期、微血管侵犯、腫瘤大體形態分型為4型是影響肝癌患者預後的獨立危險因素(RR=3.646,2.397,1.617,95％可信區間:1.042 ～ 12.713,1.063 ～5.403,1.119 ～2.337,P＜0.05).結論 肝癌的大體形態分型可能與患者臨床病理因素相關,浸潤型肝癌患者術前AFP高、術中齣血量大、微血管侵犯髮生率高,預後差.T3～T4期、微血管侵犯、腫瘤大體形態分型為浸潤型是影響肝癌患者預後的獨立危險因素.
목적 탐토간세포암(이하간칭간암)대체형태분형여환자림상병리특정급예후적관계,이급영향간암환자예후적상관인소.방법 회고성분석2008년1월지2013년12월남경대학의학원부속고루의원수치적119례간암환자적림상자료.장수술절제표본연관상위절성후도약1 cm적절편병박조,기록병이학특점.삼조문헌,결합림상경험,장간암수술절제표본대체형태분위결절형(1형)、결절돌기형(2형)、결절융합형(3형)、침윤형(4형).비교4충류형환자적림상병리인소.채용문진급전화방식진행수방,수방시간절지2014년4월혹환자사망.정태분포적계량자료이x±s표시,다조간비교채용방차분석,량량비교채용LSD-t검험;편태분포수거이M(P25,P75)표시,다조간비교채용Kruskal-Wallis검험,량량비교채용Mann-Whitney검험.계수자료비교화단인소분석채용x2검험혹Fisher학절개솔법.채용Kaplan-Meier법회제생존곡선,Log-rank검험진행생존분석.채용COX축보회귀모형진행다인소분석.결과 119례간암환자중,1형점20.17％ (24/119),2형점25.21％ (30/119),3형점21.85％(26/119),4형점32.77％(39/119).4충불동대체형태분형적간암환자년령、HBsAg양성、술전AFP、수술시간、술중출혈량、주원시간、T분기、미혈관침범비교,차이균유통계학의의(F =4.499,x2=2.944,3.516,F=1.028,2.837,2.419,x2=6.606,12.732,P＜0.05).진일보량량비교:환자술전AFP,4형현저고우3형、2형화1형,차이균유통계학의의(Z=2.183,1.851,2.083,P＜0.05).환자수술시간,4형현저장우3형화1형,차이균유통계학의의(t=1.825,1.758,P＜0.05);4형여2형비교,차이무통계학의의(t=1.521,P＞0.05).환자술중출혈량,4형현저다우3형、2형화1형,차이균유통계학의의(t=1.769,1.875,2.205,P＜0.05).환자주원시간,4형현저장우2형화1형,차이균유통계학의의(t=2.159,1.975,P＜0.05);4형여3형비교,차이무통계학의의(t=0.248,P＞0.05).환자미혈관침범,4형현저다우3형、2형화1형,차이균유통계학의의(x2=5.905,8.291,4.729,P＜0.05).119례간암환자중,116례술후획득수방,수방솔위97.48％(116/119),중위수방시간위26개월(4～74월).119례환자총체중위생존시간위25개월(1～73개월),1、3、5년총체생존솔분별위83.2％、70.7％、63.4％;무류중위생존시간위14개월(1～70개월),1、3、5년무류생존솔분별위73.3％、42.7％、11.4％.1형간암환자총체중위생존시간위56개월(51 ～61개월),1、3、5년총체생존솔분별위94.1％、82.5％、65.3％,무류중위생존시간위48개월(41 ～54개월),1、3、5년무류생존솔분별위81.3％、66.7％、58.6％;2형간암환자총체중위생존시간위56개월(52 ～ 60개월),1、3、5년총체생존솔분별위91.6％、82.6％、82.6％,무류중위생존시간위46개월(40～51개월),1、3、5년무류생존솔분별위81.4％、64.1％、64.1％;3형간암환자총체중위생존시간위53개월(48 ～58개월),1、3、5년총체생존솔분별위91.6％,84.7％,77.8％,무류중위생존시간위42개월(36 ～48개월),1、3、5년무류생존솔분별위80.1％、62.3％、50.0％;4형간암환자총체중위생존시간위46개월(40 ～51개월),1、3、5년총체생존솔분별위65.7％、51.5％、45.6％,무류중위생존시간위29개월(23 ～34개월),1、3、5년무류생존솔분별위64.3％、31.6％、22.3％.불동대체형태분형간암환자예후(총체생존솔화무류생존솔)비교,차이유통계학의의(x2=7.971,7.652,P＜0.05).환자예후(총체생존솔화무류생존솔)4형현저차우3형、2형화1형,차이균유통계학의의(총체생존솔:x2=4.823,6.131,5.785,P＜0.05;무류생존솔:x2=5.184,5.634,9.262,P＜0.05).단인소분석결과현시:술전AFP、T분기、미혈관침범、종류대체형태분형시영향간암환자예후적상관인소(x2=3.516,6.687,6.165,7.974,P＜0.05).다인소분석결과현시:T3 ～T4기、미혈관침범、종류대체형태분형위4형시영향간암환자예후적독립위험인소(RR=3.646,2.397,1.617,95％가신구간:1.042 ～ 12.713,1.063 ～5.403,1.119 ～2.337,P＜0.05).결론 간암적대체형태분형가능여환자림상병리인소상관,침윤형간암환자술전AFP고、술중출혈량대、미혈관침범발생솔고,예후차.T3～T4기、미혈관침범、종류대체형태분형위침윤형시영향간암환자예후적독립위험인소.
Objective To investigate the relationship between morphologic classification of hepatocellular carcinoma and clinicopathological features and prognosis in patients,as well as the factors affecting the prognosis of patients.Methods The clinical data of 119 patients with hepatocellular carcinoma who received surgical treatment at the Drum Tower Hospital from January 2008 to December 2013 were retrospectively analyzed.The tumors of all the patients were cut into sections with thickness of 1 cm in a coronal plane and were taken pictures for recording pathological features.The sections of tumors were divided into 4 types according to the references and clinical experiences:single nodular type (type 1),single nodular with extranodular growth type (type 2),confluent multinodular type (type 3) and infiltrating type (type 4).The clinicopathological features of patients with 4 types of tumors were compared.Patients were followed up via outpatient examination and telephone interview up to April 2014 or death.Data with normal distribution were presented as x ± s.Comparison among groups was evaluated with the repeated measures ANOVA and done by the Kruskal-Wallis method.Pairwise comparison was analyzed using LSD-t test and Mann-Whitney test.Data with skew distribution were presented as M(P25,P75).Count data and univariate analysis were done using chi-square test or Fisher exact probability.Survival curve was drawn by Kaplan-Meier method.Survival analysis were done using the Log-rank test,and multivariate analysis was done using the COX regression model.Results Of the 119 patients with hepatocellular carcinoma,20.17％ patients (24/119) were in type 1,25.21％ patients (30/119) in type 2,21.85％ patients (26/119) in type 3 and 32.77％ patients (39/119) in type 4.The age,positive HBsAg,preoperative alpha fetoprotein (AFP),operation time,volume of blood loss,duration of hospital stay,T stage and microvascular invasion in the patients with hepatocellular carcinoma of the 4 types were compared,showing significant differences (F =4.499,x2 =2.944,3.516,F =1.028,2.837,2.419,x2 =6.606,12.732,P ＜ 0.05).The preoperative AFP of the patients in type 4 was significantly higher than that in type 3,type 2 and type 1 (Z =2.183,1.851,2.083,P ＜ 0.05).The operation time of patients in type 4 was significantly longer than that in type 3 and type 1 (t =1.825,1.758,P ＜ 0.05),and was no significantly different from that in type 2 (t =1.521,P ＞ 0.05).The volume of intraoperative blood loss of the patients in type 4 was obviously more than that in type 3,type 2 and type 1 (t =1.769,1.875,2.205,P ＜ 0.05).The duration of hospital stay of patients in type 4 was significantly longer than that in type 2 and type 1 (t =2.159,1.975,P ＜ 0.05),and was no significantly different from that in type 3 (t =0.248,P ＞ 0.05).The microvascular invasion of the patients in type 4 was significantly more than that in type 3,type 2 and type 1 (x2 =5.905,8.291,4.729,P ＜ 0.05).Of the 119 patients,116 patients were followed up with a follow-up rate of 97.48％ (116/119),and the median time of follow-up was 26 months (range,4-74 months).The median overall survival time of 119 patients was 25 months (range,1-73 months).The 1-,3-,5-year overall survival rates were 83.2％,70.7％ and 63.4％,respectively.The tumor free median survival time was 14 months (range,1-70 months).The 1-,3-,5-year tumor free survival rates were 73.3％,42.7％ and 11.4％,respectively.The median overall survival time of 24 patients in type 1 was 56 months (range,51-61 months),the 1-,3-,5-year overall survival rates were 94.1％,82.5％ and 65.3％,respectively,the tumor free median survival time was 48 months (range,41-54 months),and the 1-,3-,5-year tumor free survival rates were 81.3％,66.7％ and 58.6％,respectively.The median overall survival time of 30 patients in type 2 was 56 months (range,52-60 months),the 1-,3-,5-year overall survival rates were 91.6％,82.6％ and 82.6％,respectively,the tumor free median survival time was 46 months (range,40-51 months),and the 1-,3-,5-year tumor free survival rates were 81.4％,64.1％ and 64.1％,respectively.The median overall survival time of 26 patients in type 3 was 53 months (range,48-58 months),the 1-,3-,5-year overall survival rates were 91.6％,84.7％ and 77.8％,respectively,the tumor free median survival time was 42 months (range,36-48 months),and the 1-,3-,5-year tumor free survival rates were 80.1％,62.3％ and 50.0％,respectively.The median overall survival time of 39 patients in type 4 was 46 months (range,40-51 months),the 1-,3-,5-year overall survival rates were 65.7％,51.5％ and 45.6％,respectively,the tumor free median survival time was 29 months (range,23-34 months),and the 1-,3-,5-year tumor free survival rates were 64.3％,31.6％ and 22.3％,respectively.There was a significant difference between the overall survival rates and the tumor free survival rates in the patients with morphologic classification of hepatocellular carcinoma (x2=7.971,7.652,P ＜ 0.05).The overall survival rates and tumor free survival rates of the patients in type 4 were significantly different from those in type 3,type 2 and type 1 (overall survivalrates:x2 =4.823,6.131,5.785,P ＜ 0.05 ; tumor free survival rates:x2 =5.184,5.634,9.262,P ＜ 0.05).The results of univariate analysis showed that preoperative AFP,T stage,microvascular invasion and morphologic classification of hepatocellular carcinoma were related factors affecting the prognosis of patients (x2 =3.516,6.687,6.165,7.974,P ＜ 0.05).The results of multivariate analysis showed that T3-T4 stage,microvascular invasion and hepatocellular carcinoma in type 4 were the independent risk factors affecting the prognosis of patients (RR =3.646,2.397,1.617,95％ confidence interval:1.042-12.713,1.063-5.403,1.119-2.337,P ＜ 0.05).Conclusions The morphologic classification of hepatocellular carcinoma may be associated with the clinicopathological factors of patients.The patients with infiltrating hepatocellular carcinoma have the high level of preoperative AFP,much intraoperative blood loss,high incidence of microvascular invasion and poor prognosis.The T3-T4 Stage,microvascular invasion and infiltrating type of morphological classification are the independent risk factors affecting the prognoses of patients with hepatocellular carcinoma.
