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1 中华消化外科杂志 2017 年 3 月第 16 卷第 3 Chin J Dig Surg, March 2017,Vol.16,No 论著转化手术治疗 Ⅳ 胃癌的临床疗效梁品曹亮贾帅胡祥摘要目的探讨转化治疗后手术治疗 Ⅳ 胃癌的临床疗效方法采用回顾性队列研究方法收集 2012 年 1 月至 2016 年 6 月大连医科大学附属第一医院收治的 50 例 Ⅳ 胃癌的患者的临床病理资料 50 例患者均为单一远处转移, 均进行化疗, 其中 21 例患者化疗后具备手术指征, 行胃切除术 ( R 0 切除或 R 1 切除 ), 设为转化手术治疗组 ;29 例化疗后评估无手术指征, 仅给予化疗, 设为单纯化疗组患者行 S 1+ 奥沙利铂方案或 S 1+ 多西他赛方案化疗化疗后患者行开腹远端或全胃切除术观察指标 :(1) 化疗疗效评估 ( 完全缓解部分缓解疾病稳定疾病进展病例数 ), 不良反应分级 (2) 转化手术治疗组患者的术中及术后情况 : 手术方式, 术中情况 ( 手术时间术中出血量淋巴结清扫数目手术切缘 ) 和术后情况 ( 术后并发症术后住院时间 ) (3) 两组患者的随访和生存情况比较 (4) 影响 Ⅳ 胃癌患者预后的因素分析采用门诊信件和电话等方式进行随访了解患者术后生存情况记录的生存时间是自手术当日至末次随访时间或死亡时间随访时间截至 2016 年 9 月正态分布的计量资料以 x±s 表示计数资料比较和单因素分析采用 χ 2 检验等级资料采用非参数检验采用 Kaplan Meier 法计算生存率, 生存分析比较采用 Log rank 检验采用 COX 比例风险模型进行多因素分析结果 (1) 化疗疗效评估 :50 例患者中, 24 例采用 S 1+ 奥沙利铂方案,26 例采用 S 1+ 多西他赛方案转化手术治疗组 21 例患者化疗后, 腹膜转移均阴性淋巴结转移 N2 以内 ( 第 16 组淋巴结消失或缩小 ) 肿瘤浸润深度 <T4b 肝转移明显缩小或消失术前中位化疗周为 4 2 个周 (2 0~ 9 0 个周 ) 21 例患者对化疗反应为 :15 例部分缓解,6 例疾病稳定单纯化疗组 29 例患者化疗后不符合手术指征, 未行手术治疗一线化疗的中位化疗周为 5 5 个周 (2 0~ 10 0 个周 ) 29 例患者对化疗反应为 :13 例部分缓解,11 例疾病稳定,5 例疾病进展 50 例患者化疗不良反应 :26 例 WBC 减少, 其中 6 例为 Ⅲ ~ Ⅳ 级 ;29 例中性粒细胞减少, 其中 12 例为 Ⅲ ~ Ⅳ 级 ;18 例贫血, 其中 6 例为 Ⅲ~ Ⅳ 级 ;12 例 PLT 减少, 其中 2 例为 Ⅲ~ Ⅳ 级 ;27 例厌食症, 其中 5 例为 Ⅲ ~ Ⅳ 级 ;7 例口腔炎 ;9 例腹泻 ;3 例 Cr 升高 ;4 例手足综合征 ;3 例神经感觉异常无化疗相关死亡发生 (2) 转化手术治疗组患者的术中及术后情况 : 转化手术治疗组 21 例患者中,8 例行根治性全胃切除 +D 3 淋巴结廓清术,6 例行根治性远端胃切除 +D 3 淋巴结清扫术,7 例行根治性远端胃切除 +D 2 淋巴结清扫术 ( 包括 4 例联合肝脏转移瘤切除 1 例肝转移瘤 RFA) 21 例患者的手术时间为 ( 216 ± 31) min, 术中出血量为 (128±52)mL, 淋巴结清扫数目为 (31±8) 枚,17 例 R 0 切除,4 例 R 1 切除 (3 例胃切缘阳性 1 例肝脏切缘阳性 ) 术后胃肠功能恢复时间为 (3 0±0 7) d 无死亡患者 21 例患者中 7 例出现术后并发症, 其中胰瘘 2 例腹腔出血 1 例肠梗阻 1 例肺炎 1 例腹腔感染 1 例切口感染 1 例, 均经保守治疗后痊愈出院 21 例患者术后住院时间为 (13 0±3 0)d (3) 两组患者的随访和生存情况比较 :50 例患者均获得随访, 随访时间为 6~ 46 个月, 中位随访时间为 24 个月转化手术治疗组和单纯化疗组患者 3 年累积生存率分别为 33 3% 和 6 9%, 两组比较, 差异有统计学意义 (χ 2 = 7 678,P<0 05) 进一步分析结果显示 : 转化手术治疗组 21 例患者中 17 例 R 0 切除患者生存时间为 (25 3± 2 8) 个月,4 例 R 1 切除患者生存时间为 ( 8 3± 0 9) 个月, 两者比较, 差异有统计学意义 (χ 2 = ,P<0.05) (4) 影响 Ⅳ 胃癌患者预后的因素分析 : 单因素分析结果显示 : 肿瘤 T 分 N 分化疗疗效评估化疗后手术及肿瘤根治程度是影响 Ⅳ 胃癌患者预后的相关因素 (χ 2 = 5 288,12 645,25 581,8 372,12 001,P<0.05) 多因素分析结果显示 : 转化治疗后肿瘤根治程度为 R 1 切除是 Ⅳ 胃癌患者预后不良的独立危险因素 (HR = ,95% 可信区间 :1 928 ~ ,P<0 05) 结论 Ⅳ 胃癌患者进行转化治疗后行根治性手术可提高患者生存率, 转化治疗后肿瘤根治程度为 R 1 切除是 Ⅳ 胃癌患者预后不良的独立危险因素关键词胃肿瘤,Ⅳ ; 转化治疗 ; 外科手术 ; 化疗基金项目 : 国家自然科学基金 ( ) DOI: / cma.j.issn 作者单位 : 大连医科大学附属第一医院胃肠外科通信作者 : 胡祥, g.shuxian@ aliyun.com

2 246 中华消化外科杂志 2017 年 3 月第 16 卷第 3 Chin J Dig Surg, March 2017,Vol.16,No.3 Clinical efficacy of surgical treatment for stage Ⅳ gastric cancer after conversion therapy Liang Pin, Cao Liang, Jia Shuai, Hu Xiang. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian , Liaoning Province, China Corresponding author: Hu Xiang, g.shuxian@ aliyun.com Abstract Objective To investigate the clinical efficacy of surgical treatment for stage Ⅳ gastric cancer after conversion therapy. Methods The retrospective cohort study was conducted. The clinicopathological data of 50 stage Ⅳ gastric cancer patients who were admitted to the First Affiliated Hospital of Dalian Medical University between January 2012 and June 2016 were collected. All the 50 patients who were diagnosed with single distal metastasis underwent chemotherapy. After chemotherapy, 21 patients with operation indication receiving gastrectomy ( R 0 or R 1 resection) were allocated into the conversion surgery group and 29 without operation indication continuing to chemotherapy were allocated into the chemotherapy group. Patients received S 1 + oxaliplatin or S 1 + docetaxel regimen. Patients underwent open distal or total gastrectomy. Observation indicators: (1) response assessment of chemotherapy ( complete remission, partial remission, stable disease and progressive disease), grading of of adverse reactions; ( 2) intra and post operative situations of conversion surgery group: operation procedures, intraoperative situations ( operation time, volume of blood loss, number of lymph node dissected and surgical margin) and postoperative situations ( complications and duration of hospital stay); ( 3) comparison of follow up and survival between the 2 groups; ( 4) prognostic factors analysis affecting stage Ⅳ gastric cancer patients. Follow up using outpatient examination, correspondence and telephone interview was performed to detect postoperative survival of patients up to September Survival time was from operation to the last follow up or death. Measurement data with normal distribution were represented as x±s. Comparison of count data and univariate analysis were done using the chi square test. Ordinal data were analyzed by the nonparametric test. The survival rate was calculated by the Kaplan Meier method, and the Log rank test was used for survival analysis. Multivariate analysis was done using the COX regression model. Results ( 1) Response assessment of chemotherapy: of 50 patients, 24 received S 1 + oxaliplatin regimen and 26 received S 1 + docetaxel regimen. Twenty one patients in the conversion surgery group underwent chemotherapy, with negative peritoneal metastasis, N2 and below of lymph node metastasis ( No.16 lymph node disappeared or reduced), invasive depth <T4b and narrowing or disappeared hepatic metastasis. A median preoperative chemotherapy cycle was 4 2 cycles ( range, cycles). Chemotherapy reaction of 21 patients: 15 had partial remission and 6 had stable disease. Twenty nine patients without operation indication in the chemotherapy group didn t receive surgery. The median cycle of first line chemotherapy was 5 5 cycles (range, cycles). Chemotherapy reaction of 29 patients: 13 had partial remission, 11 had stable disease and 5 patient had progressive disease. Chemotherapy adverse reactions of 50 patients: 26 had reduced white blood cells ( WBCs), including 6 with grade Ⅲ-Ⅳ of adverse reactions; 29 had reduced neutrophils, including 12 with grade Ⅲ - Ⅳ of adverse reactions; 18 had anemia, including 6 with grade Ⅲ-Ⅳ of adverse reactions; 12 had reduced platelets, including 2 with grade Ⅲ-Ⅳ of adverse reactions; 27 had apositia, including 5 with grade Ⅲ-Ⅳ of adverse reactions; 7 had stomatitis; 9 had diarrhea; 3 had elevated serum creatinin; 4 had hand foot syndrome; 3 had abnormal sensory nerve. There was no chemotherapy related death. (2) Intra and post operative situations of conversion surgery group: of 21 patients in the conversion surgery group, 8 underwent radical total gastrectomy + D 3 lymph node dissection, 6 underwent radical distal gastrectomy + D 3 lymph node dissection and 7 underwent radical distal gastrectomy + D 2 lymph node dissection ( including 4 combined with resection of hepatic metastatic tumors and 1 combined with radiofrequency ablation of hepatic metastatic tumor). Operation time, volume of blood loss, number of lymph node dissected and recovery time of gastrointestinal function of 21 patients were (216±31)minutes, (128±52)mL, 31±8 and (3 0± 0 7)days, respectively. There were 17 patients receiving R 0 resection and 4 receiving R 1 resection (3 with positive gastric margin and 1 with positive hepatic margin). There was no death. Seven of 21 patients with complications were cured by conservative treatment, including 2 with pancreatic fistula, 1 with intra abdominal hemorrhage, 1 with intestinal obstruction, 1 with pneumonia, 1 with intra abdominal infection and 1 with wound infection. Duration of hospital stay of 21 patients was (13 0±3 0)days. (3) Comparison of follow up and survival between the 2 groups: 50 patients were followed up for 6-46 months, with a median time of 24 months. The 3 year cumulative survival rates in the conversion surgery and chemotherapy groups were respectively 33 3% and 6 9%, with a statistically significant difference between the 2 groups (χ 2 = 7 678, P<0 05). Results of further analysis showed that R 0 resection of 17 patients and R 1 resection of 4 patients in the conversion surgery group were respecgtively (25 3±2 8) months and (8 3±0 9) months, with a statistically significant difference between the 2 groups (χ 2 = , P < 0 05). ( 4) Prognostic factors analysis affecting stage Ⅳ gastric cancer patients: results of univariate analysis showed that T stage, N stage, response assessment of chemotherapy, surgery after chemotherapy and degree of tumor radical resection were related factors affecting prognosis of stage Ⅳ gastric cancer patients ( χ 2 = 5 288, , , 8 372, , P < 0 05). Results of multivariate analysis showed that R 1 resection after conversion therapy was an independent risk factor affecting prognosis of stage Ⅳ gastric cancer patients (HR = , 95% confidence interval: , P<0 05). Conclusion Radical resection after conversion therapy can increase survival rate of stage Ⅳ gastric cancer patients, and R 1 resection after conversion therapy is an independent risk factor affecting poor prognosis of stage Ⅳ gastric cancer patients.

3 中华消化外科杂志 2017 年 3 月第 16 卷第 3 Chin J Dig Surg, March 2017,Vol.16,No Key words Gastric neoplasms, stage Ⅳ; Conversion therapy; Surgical procedures, operative; Chemotherapy Fund program: National Natural Science Foundation of China ( ) 全世界范围内, 胃癌占全部癌症的 1 / 4, 其病死率居癌症死亡的第 3 位 [1-3] 已经出现浸润转移的进展胃癌患者预后不良, 此时不考虑手术治疗而给予全身化疗 Ⅳ 胃癌患者的预后不良, 即使给予最佳的支持治疗, 其中位生存时间也仅有 3 ~ 5 个月 [4] SPIRITS 试验结果显示 : 行 S 1 联合顺铂治疗患者中位总体生存时间 >1 年, 因而成为日本治疗进展胃癌和复发胃癌的标准化疗方案 [5] 然而, 关于化疗后手术治疗 Ⅳ 胃癌的疗效研究很少 [6-7] 目前新的化疗方案可使部分不可切除的胃癌转化为可切除的胃癌, 患者行根治性手术, 可能延长生存时间本研究回顾性分析 2012 年 1 月至 2016 年 6 月我科收治的 50 例 Ⅳ 胃癌患者的临床病理资料, 探讨转化治疗后手术治疗 Ⅳ 胃癌的临床疗效 1 资料与方法 1.1 一般资料采用回顾性队列研究方法收集 50 例 Ⅳ 胃癌患者的临床病理资料, 其中男 31 例, 女 19 例 ; 年龄 32 ~ 69 岁, 平均年龄 55 岁 50 例患者均为单一远处转移 50 例患者均进行化疗, 其中 21 例患者化疗后具备手术指征, 行胃切除术 (R 0 切除或 R 1 切除 ), 设为转化手术治疗组 ;29 例化疗后评估无手术指征, 仅给予化疗, 设为单纯化疗组两组患者性别年龄肿瘤部位肿瘤直径 T 分 N 分肿瘤转移部位比较, 差异均无统计学意义 ( P>0.05), 具有可比性见表 1 本研究通过我院伦理委员会审批, 批号为 KY 患者及家属术前均签署手术知情同意书 1.2 纳入标准和排除标准纳入标准 :(1) 年龄 20 ~ 70 岁 (2) 术前经胃镜活组织病理学检查 CT 检查或术后病理学检查确诊为原发性进展胃腺癌, 肿瘤国际抗癌联盟 (UICC) 分为 Ⅳ (3) 既往无化疗史 (4) 能够耐受化疗药物 (5) 临床病理资料完整排除标准 :(1) 非 Ⅳ 胃癌 (2) 影像学检查发现胃癌发生多处远处转移 (3) 未能完成 6 个周化疗 (4) 既往有其他肿瘤病史 (5) 有梗阻症状消化道出血 (6) 临床病理资料不全 1.3 化疗方法及疗效评估患者行 S 1+ 奥沙利铂方案或 S 1+ 多西他赛方案化疗按照实体瘤反应评估标准, 日本胃癌协会指南进行肿瘤化疗后反应分级, 疗效分为完全缓解部分缓解疾病稳定疾病进展所有腹膜种植转移患者均经腹腔镜探查, 按照即将出版的第 15 版胃癌处理规约分类 [8] 每 4 ~ 6 周行 CT 检查, 测量评估肿瘤区域 1.4 手术指征及手术方案手术指征 :Ⅳ 胃癌经化疗后缓解降或稳定, 且估计肿瘤可根治性切除根据患者具体情况在最后 1 个周化疗后 4 ~ 6 周行胃癌根治术 D 2 或 D 3 廓清术及肝部分切除术手术均为开腹手术手术方式严格按照日本第 14 版胃癌处理规约的规定, 根据肿瘤部位选择远端或全胃切除术 [9] 消化道重建 : 远端胃切除术后采用 Billroth Ⅱ 式重建, 全胃切除术后采用 Roux en Y 吻合 1.5 观察指标 (1) 化疗疗效评估 ( 完全缓解部分缓解疾病稳定疾病进展病例数 ), 不良反应分级 (2) 转化手术治疗组患者的术中及术后情况 : 手术方式, 术中情况 ( 手术时间术中出血量淋巴结清扫数目手术切缘 ) 和术后情况 ( 术后并发症术后住院时间 ) (3) 两组患者的随访和生存情况比较 ( 4) 影响 Ⅳ 胃癌患者预后的因素分析组别例数表 1 转化手术治疗组和单纯化疗组 Ⅳ 胃癌患者化疗前的一般资料比较 ( 例 ) 性别年龄 ( 岁 ) 肿瘤部位肿瘤直径 (cm) T 分 N 分肿瘤转移部位男女 <60 60 胃上部胃中部胃下部 <5 5 T2 T3 T4 N1 N2 N3 肝脏腹膜第 16 组淋巴结转化手术治疗组单纯化疗组统计值 χ 2 = χ 2 = Z = χ 2 = Z = Z = Z = P 值 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05

4 ２４８１６中华消化外科杂志２０１７年３月第１６卷第３随访采用门诊信件和电话等方式进行随访了解患者术后生存情况记录的生存时间是自手术当日ＣｈｉｎＪＤｉｇＳｕｒｇＭａｒｃｈ２０１７Ｖｏｌ１６Ｎｏ３梗阻１例肺炎１例腹腔感染１例切口感染１例均经保守治疗后痊愈出院２１例患者术后住院时间为１３０±３０ｄ至末次随访时间或死亡时间随访时间截至２０１６年２３１７中位随访时间为２４个月转化手术治疗组和单纯９月统计学分析应用ＳＰＳＳ１３０统计软件进行分析正态分布的计量资料以ｘ ±ｓ表示计数资料比较和单因素分２ χ 析采用检验等级资料采用非参数检验采用ＫａｐｌａｎＭｅｉｅｒ法计算生存率生存分析比较采用两组患者随访和生存情况比较５０例患者均获得随访随访时间为６４６个月化疗组患者３年累积生存率分别为３３３和６９两组比较差异有统计学意义 χ ２７６７８Ｐ００５见图１Ｌｏｇｒａｎｋ检验采用ＣＯＸ比例风险模型进行多因素分析Ｐ００５为差异有统计学意义２２１结果化疗疗效评估５０例患者中２４例采用Ｓ１奥沙利铂方案２６例采用Ｓ１多西他赛方案转化手术治疗组２１例患者化疗后腹膜转移均阴性淋巴结转移Ｎ２以内第１６组淋巴结消失或缩小肿瘤浸润深度Ｔ４ｂ肝转移明显缩小或消失术前中位化疗周为４２个周２０９０个周２１例患者对图１化疗反应为１５例部分缓解６例疾病稳定单纯化疗组２９例患者化疗后不符合手术指征未行手术治疗一线化疗的中位化疗周为５５个周２０１００个周２９例患者对化疗反应为１３例部分缓解１１例疾病稳定５例疾病进展５０例患者化疗不良反应２６例ＷＢＣ减少其中６例为Ⅲ Ⅳ级２９例中性粒细胞减少其中１２例转化手术治疗组和单纯化疗组胃癌患者的累积生存曲线进一步分析结果显示转化手术治疗组２１例患者中１７例Ｒ０切除患者生存时间为２５３±２８个月４例Ｒ１切除患者生存时间为８３±０９个月两者比较差异有统计学意义 χ ２１６２４２Ｐ００５见图２为Ⅲ Ⅳ级１８例贫血其中６例为Ⅲ Ⅳ级１２例ＰＬＴ减少其中２例为Ⅲ Ⅳ级２７例厌食症其中５例为Ⅲ Ⅳ级７例口腔炎９例腹泻３例Ｃｒ升高４例手足综合征３例神经感觉异常无化疗相关死亡发生２２转化手术治疗组患者的术中及术后情况转化手术治疗组２１例患者中８例行根治性全胃切除Ｄ３淋巴结廓清术６例行根治性远端胃切除Ｄ３淋巴结清扫术７例行根治性远端胃切除Ｄ２淋巴结清扫术包括４例联合肝脏转移瘤切除１例肝转移瘤ＲＦＡ２１例患者的手术时间为２１６ ± ３１ｍｉｎ术中出血量为１２８±５２ｍｌ淋巴结清扫数图２转化手术治疗组行Ｒ０切除和Ｒ１切除胃癌患者的累积生存曲线影响 Ⅳ 胃癌患者预后的单因素和多因素分析目为３１±８枚１７例Ｒ０切除４例Ｒ１切除３例胃２４时间为３０±０７ｄ无死亡患者２１例患者中７例疗疗效评估化疗后手术及肿瘤根治程度是影响切缘阳性１例肝脏切缘阳性术后胃肠功能恢复出现术后并发症其中胰瘘２例腹腔出血１例肠单因素分析结果显示肿瘤Ｔ分Ｎ分化 Ⅳ胃癌患者预后的相关因素见表２

5 中华消化外科杂志 2017 年 3 月第 16 卷第 3 Chin J Dig Surg, March 2017,Vol.16,No 表 2 影响 50 例 Ⅳ 胃癌患者预后的单因素分析表 3 影响 50 例 Ⅳ 胃癌患者预后的多因素分析临床病理因素赋值例数性别 3 年生存率 (%) 男女年龄 ( 岁 ) < 肿瘤部位胃上部 χ 2 值 P 值 > >0.05 胃中部 >0.05 胃下部肿瘤直径 (cm) < T 分 T >0.05 T <0.05 T N 分 N N N 肿瘤转移部位肝脏 <0.05 腹膜 >0.05 第 16 组淋巴结化疗疗效评估部分缓解疾病稳定 <0.05 疾病进展化疗后手术是否 a 肿瘤根治程度 R R < <0.05 注 : a 50 例患者行化疗后仅有 21 例符合手术指征, 行化疗后手术治疗多因素分析结果显示 : 转化治疗后肿瘤根治程度为 R 1 切除是 Ⅳ 胃癌患者预后不良的独立危险因素见表 3 临床病理因素 b 值标准误 Wald 值 HR 值 95% 可信区间 P 值 T 分 ~ >0.05 N 分 ~2.967 >0.05 化疗疗效评估 ~8.839 >0.05 化疗后手术 ~7.624 >0.05 a 肿瘤根治程度 ~ <0.05 注 : a 50 例患者行化疗后仅有 21 例符合手术指征, 行化疗后手 3 讨论术治疗进展胃癌复发胃癌的治疗不断发展, 多种治疗策略应运而生, 改善了患者的生存率 [10] Ⅳ 胃癌预后差, 美国国立综合癌症网络 (NCCN) 指南日本胃癌处理规约均推荐以全身化疗为主的姑息治疗 [11-12] 然而, 随着化疗方案的进步, 部分 Ⅳ 胃癌患者生存时间延长, 且部分患者经转化治疗后, 具备根治性胃癌切除术的指征, 行手术治疗可以进一步延长生存时间 [13-14] 转化治疗与新辅助治疗不同, 新辅助治疗是针对局部进展胃癌而无脏器转移的患者, 其目的是使肿瘤降, 从而提高 R 0 切除率, 并同时治疗微转移灶而 Ⅳ 胃癌的转化治疗是指通过化疗放疗靶向介入等治疗手段, 使 Ⅳ 胃癌部分缓解或者完全缓解, 对部分适合根治性手术切除的患者行手术治疗, 以延长患者生存时间并提高其生命质量本研究分别采用 S 1+ 奥沙利铂及 S 1+ 多西他赛方案, 临床反应率及疾病控制率较高, 与其他研究结果相近 [15-17] 本研究结果显示 : 目前的化疗方案对腹膜转移为 P1c 患者的转化治疗效果欠佳日本第 15 版规约对于腹膜转移的详细分类, 有助于评估腹膜转移患者转化治疗的效果本研究结果显示 :Ⅳ 胃癌化疗后手术并发症与普通腹部手术比较, 差异无统计学意义, 其安全性显著本研究中少数患者出现胰瘘, 胰瘘程度轻, 经保守治疗后痊愈胰瘘的发生可能与化疗引起的组织水肿胰腺周围淋巴结清扫有关, 值得临床重视并预防本研究中无死亡患者, 笔者团队的经验提示 : Ⅳ 胃癌化疗后手术治疗不会增加手术风险, 具有安全性运用双极电凝及超声刀等手段可确保彻底清扫及减少副损伤本研究结果显示 : 对于 Ⅳ 胃癌化疗后, 行手术治疗的患者其生存情况显著优于非手术治疗的患者进一步分析结果显示 : 转化治疗后行手术治疗的患者中,R 0 切除患者的中位生存时间明显长于

6 250 中华消化外科杂志 2017 年 3 月第 16 卷第 3 Chin J Dig Surg, March 2017,Vol.16,No.3 R 1 切除患者多因素分析结果显示 :R 0 切除是预后的独立影响因素,Ⅳ 胃癌化疗后行 R 0 切除能显著延长患者生存时间, 与已有文献报道相同 [18] Ito [19] 等的研究结果显示 :Ⅳ 胃癌经转化治疗后,R 0 切除的患者中位生存时间与非 R 0 切除的患者比较, 差异有统计学意义另有研究结果显示 : 单一不可切除因素化疗反应率高 R 0 切除是影响转化治疗延长 Ⅳ 胃癌患者术后生存时间的重要因素转化手术 R 0 切除后 5 年总生存率明显高于单纯化疗患者, 而非 R 0 切除并不能使患者生存获益 [20-22] 以上几项研究的样本量小, 结论尚需要大样本数据验证但上述研究结果都提示 Ⅳ 胃癌转化治疗后, R 0 切除可延长患者生存时间转化治疗可以提高部分 Ⅳ 胃癌患者的预后, 有可能成为 Ⅳ 胃癌的重要治疗方法对于转化治疗的时机把握转化手术指征转化治疗效果评价等问题的探讨, 还有待大样本临床随机对照试验提供循证医学证据参考文献 [1] Crew KD, Neugut AI. Epidemiology of gastric cancer[ J]. World J Gastroenterol,2006,12 ( 3): DOI: / wjg. v12. i [2] Jemal A, Bray F, Center MM, et al. Global cancer statistics[ J]. CA Cancer J Clin, 2011, 61 ( 2 ): DOI: / caac [3] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics,2012 [J]. CA Cancer J Clin, 2015, 65 ( 2): DOI: / caac [4] Glimelius B, Ekström K, Hoffman K, et al. Randomized compari son between chemotherapy plus best supportive care with best sup portive care in advanced gastric cancer [ J]. Ann Oncol,1997,8 (2): [5] Koizumi W, Narahara H, Hara T, et al. S 1 plus cisplatin versus S 1 alone for first line treatment of advanced gastric cancer ( SPIR ITS trial): a phase Ⅲ trial[ J]. Lancet Oncol,2008,9(3): DOI: / S (08) [ 6] Nakajima T, Ota K, Ishihara S, et al. Combined intensive chemo therapy and radical surgery for incurable gastric cancer[ J]. Ann Surg Oncol,1997,4(3): DOI: / bf [7] Suzuki T, Tanabe K, Taomoto J, et al. Preliminary trial of adju vant surgery for advanced gastric cancer[ J]. Oncol Lett,2010,1 (4): DOI: / ol_ [8] 胡祥. 日本胃癌处理规约及胃癌治疗指南变更的新动态 [J]. 中国实用外科杂志,2016,36(6): DOI: / CJPS.ISSN [9] Japanese Gastric Cancer Association. Japanese classification of gas tric carcinoma: 3rd English edition[ J]. Gastric Cancer,2011,14 (2): DOI: / s [10] Boku N, Yamamoto S, Fukuda H, et al. Fluorouracil versus com bination of irinotecan plus cisplatin versus S 1 in metastatic gastric cancer: a randomised phase 3 study[ J]. Lancet Oncol,2009,10 (11): DOI: / S (09) [11] Chen XL, Chen XZ, Yang C, et al. Docetaxel, cisplatin and flu orouracil ( DCF ) regimen compared with non taxane containing palliative chemotherapy for gastric carcinoma: a systematic review and meta analysis[ J]. PLoS One,2013,8( 4):e DOI: / journal.pone [12] Sano T, Aiko T. New Japanese classifications and treatment guide lines for gastric cancer: revision concepts and major revised points [ J ]. Gastric Cancer, 2011, 14 ( 2 ): DOI: / s [13] Inoue K, Nakane Y, Kogire M, et al. Phase Ⅱ trial of preopera tive S 1 plus cisplatin followed by surgery for initially unresectable locally advanced gastric cancer [ J]. Eur J Surg Oncol,2012,38 (2): DOI: / j.ejso [14] Kim SW. The result of conversion surgery in gastric cancer patients with peritoneal seeding[ J]. J Gastric Cancer,2014,14( 4): DOI: / jgc [ 15] Kitayama J, Ishigami H, Yamaguchi H, et al. Salvage gastrectomy after intravenous and intraperitoneal paclitaxel ( PTX) administra tion with oral S 1 for peritoneal dissemination of advanced gastric cancer with malignant ascites[ J]. Ann Surg Oncol,2014,21( 2): DOI: / s y. [16] Koizumi W, Kim YH, Fujii M, et al. Addition of docetaxel to S 1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study ( START) [ J]. J Cancer Res Clin Oncol,2014,140(2): DOI: / s [17] Zhong DT, Wu RP, Wang XL, et al. Combination Chemotherapy with S 1 and Oxaliplatin ( SOX) as First Line Treatment in Elderly Patients with Advanced Gastric Cancer [ J]. Pathol Oncol Res, 2015,21(4): DOI: / s [ 18] Tanizawa Y, Terashima M, Tokunaga M, et al. Conversion therapy of stage Ⅳ gastric cancer[ J]. Gan To Kagaku Ryoho,2012,39 (13): [19] Ito S, Oki E, Nakashima Y, et al. Clinical significance of adju vant surgery following chemotherapy for patients with initially unre sectable stage Ⅳ gastric cancer [ J]. Anticancer Res, 2015, 35 (1): [20] Yamamoto M, Sakaguchi Y, Matsuyama A, et al. Surgery after preoperative chemotherapy for patients with unresectable advanced gastric cancer [ J]. Oncology, 2013, 85 ( 4): DOI: / [21] Fukuchi M, Ishiguro T, Ogata K, et al. Prognostic Role of Con version Surgery for Unresectable Gastric Cancer [ J]. Ann Surg Oncol,2015, 22 ( 11 ): DOI: / s [22] Kinoshita J, Fushida S, Tsukada T, et al. Efficacy of conversion gastrectomy following docetaxel, cisplatin, and S 1 therapy in po tentially resectable stage Ⅳ gastric cancer[ J]. Eur J Surg Oncol, 2015,41(10): DOI: / j.ejso ( 收稿日 : ) ( 本文编辑 : 夏浪 )

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5-25袁宏钧.indd 第 24 卷第 5 期 2015 年 5 月碘 131 doi:10.3978/j.issn.1005-6947.2015.05.005 http://dx.doi.org/10.3978/j.issn.1005-6947.2015.05.005 Chinese Journal of General Surgery, 2015, 24(5):643 647. Chinese Journal of