中国胆囊癌流行病学特征与诊治 及预后分析(附6159例报告)

Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases

  • 摘要: 目的 探讨 2010—2017 年中国胆囊癌临床流行病学特征、诊断、治疗与预后情况。 方法 采用单病种回顾性登记队列研究方法。基于“真实世界研究”理念,收集2010年1月至2017年 12月中国胆囊癌研究小组(CRGGC)建立的中国胆囊癌多中心回顾性临床资料数据库中42家医院收 治的 6 159例胆囊癌患者的临床病理资料。观察指标:(1)病例来源情况。(2)年龄与性别分布情况。 (3)诊断情况。(4)外科治疗与预后情况。(5)综合治疗与预后情况。随访数据由CRGGC对各协作中心 的临床随访数据进行收集整理,主要结局指标为手术治疗患者手术之日或未手术患者确诊之日起,至 结局事件发生或随访截至时间的总体生存时间。正态分布的计量资料以x±s表示,组间比较采用t检 验;偏态分布的计量资料以M(Q1,Q3)或M(范围)表示,组间比较采用U检验。计数资料以绝对数和 (或)百分比表示,组间比较采用χ2检验。单因素分析采用强迫引入Logistic回归模型,将P<0.1的因素 引入多因素分析。多因素分析采用逐步后退 Logistic 回归模型。采用寿命表法计算生存率,采用 Kaplan?Meier法绘制生存曲线,采用Log?rank检验进行生存分析。结果  (1)病例来源情况:42家医院 中,三级甲等医院35家,三级乙等医院7家;胆囊癌收治高流量医院16家,非高流量医院26家。42家 医院地域分布:中部地区9家,东北地区5家,东部地区22家,西部地区6家。6 159例患者地域分布: 2 154例(34.973%)来自中部地区,705例(11.447%)来自东北地区,1 969例(31.969%)来自东部地区, 1 331例(21.611%)来自西部地区。6 159例患者总体院均诊断与治疗数为(18.3±4.5)例/年;其中4 974例 (80.760%)来源于高流量医院,院均诊断与治疗患者数为(38.8±8.9)例/年;1 185例(19.240%)来源于 非高流量医院,院均诊断与治疗患者数为(5.7±1.9)例/年。(2)年龄与性别分布情况:6 159例患者确诊 年龄为64(56,71)岁;其中男性2 247例(36.483%),确诊年龄为64(58,71)岁;女性3 912例(63.517%), 确诊年龄为 63(55,71)岁。性别比例为女性:男性=1.74∶1。3 886 例(63.095%)患者确诊年龄为 56~ 75岁。不同性别患者确诊年龄比较,差异有统计学意义(Z=-3.99,P<0.001)。(3)诊断情况:6 159例患 者中,初步诊断为胆囊癌 2 503 例(40.640%),初步诊断非胆囊癌 3 656 例(59.360%)。未手术患者 2 110例(34.259%),其中初步诊断为胆囊癌200例(9.479%),初步诊断为非胆囊癌1 910例(90.521%)。 手术患者4 049例(65.741%),其中初步诊断为胆囊癌2 303例(56.878%),初步诊断为非胆囊癌1 746例 (43.122%)[术中诊断为胆囊癌 774 例(19.116%)、术后诊断为胆囊癌 972 例(24.006%)]。6 159 例患 者中,初步诊断前行超声、CT、磁共振成像(MRI)检查分别为2 521例(40.932%)、2 335例(37.912%)、 1 114 例(18.087%),行血清癌胚抗原(CEA)、CA19?9、CA125 检测分别为 3 259 例(52.914%)、3 172 例 (51.502%)、4 016例(65.205%)。同一例患者可行多种检查。单因素分析结果显示:来源医院地区(东 部地区、西部地区),年龄(≥72岁),收治医院胆囊癌患者流量,初步诊断前超声检查,初步诊断前 CT 检查,初步诊断前 MRI 检查,初步诊断前 CEA 检测,初步诊断前血清 CA19?9 检测,初步诊断前血清 CA125检测均是影响胆囊癌患者初步诊断为胆囊癌的相关因素(优势比=1.45、1.98,0.69,0.68,2.43, 0.41,1.63,0.41,0.39,0.42,95%可信区间为1.21~1.74、1.64~2.40,0.59~0.80,0.60~0.78,2.19~2.70,0.37~ 0.45,1.43~1.86,0.37~0.45,0.35~0.43,0.38~0.47,P<0.05)。多因素分析结果显示:来源医院地区(东 部地区、西部地区),性别,年龄(≥72岁),收治医院胆囊癌患者流量,初步诊断前超声检查,初步诊断 前CT检查,初步诊断前血清CA19?9检测是影响胆囊癌患者初步诊断为胆囊癌的独立影响因素(优势 比=1.36、1.42,0.89,0.67,1.85,1.56,1.57,0.39,95% 可信区间为 1.13~1.64、1.16~1.73,0.79~0.99,0.57~ 0.78,1.60~2.14,1.38~1.77,1.38~1.79,0.35~0.43,P<0.05)。(4)外科治疗与预后情况:4 049例手术治疗 患者中,2 447例(60.435%)分期资料和随访资料完整,0期、Ⅰ期、Ⅱ期、Ⅲa期、Ⅲb期、Ⅳa期、Ⅳb期分别为 85 例(3.474%)、201 例(8.214%)、71 例(2.902%)、890 例(36.371%)、382 例(15.611%)、33 例 (1.348%)、785例(32.080%)。2 447例患者中位随访时间为55.75个月(95%可信区间为52.78~58.35), 术后总体中位生存时间为23.46个月(95%可信区间为21.23~25.71)。0期、Ⅰ期、Ⅱ期、Ⅲa期、Ⅲb期、 Ⅳa期、Ⅳb期患者总体生存情况比较,差异有统计学意义(χ2=512.47,P<0.001)。4 049例手术治疗患 者中,可切除性肿瘤 2 988例(73.796%),不可切除性肿瘤 177例(4.371%),可切除性无法评估 884例 (21.833%)。2 988 例可切除性肿瘤患者中,根治性切除 2 036 例(68.139%),非根治性切除 504 例 (16.867%),手术根治性无法评估 448 例(14.994%)。2 447 例分期和随访资料完整的手术治疗患者 中,不可切除性肿瘤 53例(2.166%),可切除性肿瘤非根治性切除 300例(12.260%),可切除性肿瘤根 治性切除1 441例(58.888%),无法评估653例(26.686%)。733例未手术患者随访资料完整。未手术、 不可切除性肿瘤手术治疗、可切除性肿瘤非根治性切除、可切除性肿瘤根治性切除患者总体生存情况 比较,差异有统计学意义(χ2=121.04,P<0.001)。(5)综合治疗与预后情况:6 159 例患者中,541 例 (8.784%)行术后辅助化疗和晚期化疗,76例(1.234%)行放疗。1 170例进展期(Ⅲa期及以上)行根治 性切除手术患者中,联合术后辅助化疗126例(10.769%),未联合术后辅助化疗1 044例(89.231%),两 者总体生存情况比较,差异无统计学意义(χ2=0.23,P=0.629)。658 例Ⅲa 期行根治性切除手术患者 中,联合术后辅助化疗66例(10.030%),未联合术后辅助化疗592例(89.970%),两者总体生存情况比 较,差异无统计学意义(χ2=0.05,P=0.817)。512例≥Ⅲb期行根治性切除手术患者中,联合术后辅助化 疗 60例(11.719%),未联合术后辅助化疗452例(88.281%),两者总体生存情况比较,差异无统计学意义 (χ2=1.50,P=0.220)。结论 我国胆囊癌患者女性多于男性,超过半数确诊年龄为56~75岁。初步诊断 前行超声和CT检查、血清CA19?9检测是初步诊断胆囊癌的独立影响因素,基于术前可切除性评估可 改进治疗决策、改善患者预后。我国胆囊癌辅助化疗尚不规范且比例较低。

     

    Abstract: Objective To investigate the epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China from 2010 to 2017. Methods The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected.Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(Q1,Q3) or M(range), and comparison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P< 0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results (1) Case resources: of the 42 hospitals, there were 35 class A of  tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56, 71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients (Z=?3.99, P< 0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as nongallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as nongallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients (odds ratio= 1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21?1.74, 1.64? 2.40, 0.59?0.80, 0.60?0.78, 2.19?2.70, 0.37?0.45, 1.43?1.86, 0.37?0.45, 0.35?0.43, 0.38?0.47, P< 0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were independent influencing factors influencing initial diagnosis of gallbladder cancer patients (odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13?1.64, 1.16?1.73, 0.79?0.99,0.57?0.78, 1.60?2.14, 1.38?1.77, 1.38?1.79, 0.35?0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78 ? 58.35) and 23.46 months (95% confidence interval as 21.23 ? 25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb (χ 2 =512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases (68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor (χ2 =121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy (χ2 =0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲ a who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy (χ2 =0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without postoperative adjuvant chemo-therapy (χ2 =1.50, P=0.220). Conclusions There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

     

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