FOLFOX-6与肝动脉灌注化疗对结直肠癌肝转移治疗效果的比较

Objective To compare the efficacy and side effects between systemic chemotherapy and hepatic arterial infusion by combination of oxaliplatin and 5-fluorouracil (FOLFOX-6) with 5-fluorouracil in the patients who have developed hepatic metastasis after colorectal cancer operation. The factors that would affect the prognosis without operational treatment were also analyzed. Methods 46patients who had signed the informed consents were allocated into two groups: the group with general chemotherapy (Trial Group includes 26 cases) and the one with hepatic arterial infusion chemotherapy (Control Group includes 20 cases). The total effective rate, the prognosis, the cytoxicitic side effects,quality of life, the total survival rate and the responses were the main parameters determined. Kaplan-Meier was used to analyze Mono-factor to the prognostic responses and the Cox mode was used to analyze poly-factor to the prognostic responses. Results The overall survival rate was significantly higher by using systemic treatment versus HAI(median, 15. 0 v 11.2 months;P＜0.05). The difference in overall responsive rate (CR+PR) between the two groups was statistically significant (50% v 10%;P=0. 011). No significant difference was found in PS scale during the treatment. (P=0. 126). Except for myelosuppression and abdominal pain, no significant difference was found in the other side effects. Univariate analysis revealed that the invasive lesions to serosa, the distribution of liver metastases, the size and number of liver metastases, primary carcinoma involving lymph nodes and the treatment were correlated with prognoses. Cox regression analysis showed that the larger diameter of liver metastases, the number of liver lesions, primary carcinomas involved in serosal layer and the treatment modules were independent prognostic factors. Conclusions The oxaliplatin-based FOLFOX-6 chemotherapy regiment has a better responsive rate and survival rate than the traditional infusion with 5-fluorouracil to the main hepatic artery for interventional therapy. The diameter of the hepatic metastasis larger than 5em, multiple hepatic metastasis and the primary lesions penetrating serosal layer suggest the poor prognosis. The oxaliplatin-based systematic chemotherapy has a better prognosis. Therefore,it is worth carrying on further study on modification of traditional hepatic arterial infusion and on evaluation of therapy by combination of the hepatic arterial infusion with the systematic chemotherapy.     

FOLFOX-6与肝动脉灌注化疗对结直肠癌肝转移治疗效果的比较

Objective To compare the efficacy and side effects between systemic chemotherapy and hepatic arterial infusion by combination of oxaliplatin and 5-fluorouracil (FOLFOX-6) with 5-fluorouracil in the patients who have developed hepatic metastasis after colorectal cancer operation. The factors that would affect the prognosis without operational treatment were also analyzed. Methods 46patients who had signed the informed consents were allocated into two groups: the group with general chemotherapy (Trial Group includes 26 cases) and the one with hepatic arterial infusion chemotherapy (Control Group includes 20 cases). The total effective rate, the prognosis, the cytoxicitic side effects,quality of life, the total survival rate and the responses were the main parameters determined. Kaplan-Meier was used to analyze Mono-factor to the prognostic responses and the Cox mode was used to analyze poly-factor to the prognostic responses. Results The overall survival rate was significantly higher by using systemic treatment versus HAI(median, 15. 0 v 11.2 months;P＜0.05). The difference in overall responsive rate (CR+PR) between the two groups was statistically significant (50% v 10%;P=0. 011). No significant difference was found in PS scale during the treatment. (P=0. 126). Except for myelosuppression and abdominal pain, no significant difference was found in the other side effects. Univariate analysis revealed that the invasive lesions to serosa, the distribution of liver metastases, the size and number of liver metastases, primary carcinoma involving lymph nodes and the treatment were correlated with prognoses. Cox regression analysis showed that the larger diameter of liver metastases, the number of liver lesions, primary carcinomas involved in serosal layer and the treatment modules were independent prognostic factors. Conclusions The oxaliplatin-based FOLFOX-6 chemotherapy regiment has a better responsive rate and survival rate than the traditional infusion with 5-fluorouracil to the main hepatic artery for interventional therapy. The diameter of the hepatic metastasis larger than 5em, multiple hepatic metastasis and the primary lesions penetrating serosal layer suggest the poor prognosis. The oxaliplatin-based systematic chemotherapy has a better prognosis. Therefore,it is worth carrying on further study on modification of traditional hepatic arterial infusion and on evaluation of therapy by combination of the hepatic arterial infusion with the systematic chemotherapy.     

动脉微泵灌注奥沙利铂治疗结直肠癌术后肝转移

目的探讨动脉微泵灌注奥沙利铂方案TACE治疗结直肠癌术后肝转移的有效性、安全性及其影响因素。方法回顾性分析68例经病理证实且接受至少2个疗程的动脉微泵灌注奥沙利铂方案TACE治疗的结直肠癌术后肝转移患者的资料。以TACE前是否曾接受全身静脉化疗分为A组(未化疗)和B组(已化疗)。随访患者生存时间,按实体瘤的疗效评价标准评价客观疗效,对比两组的不良反应。对影响生存时间的可能因素进行Cox回归分析。结果 68例患者中位生存期(OS)为18个月,中位无进展生存时间(PFS)为10个月。经治疗后完全缓解16例,部分缓解26例,稳定21例,进展5例;治疗有效率(RR)为61.76%(42/68)。两组RR、OS、PFS差异均无统计学意义(P均0.05)。两组不良反应中程度≥Ⅰ级的发生率差异均无统计学意义(P均0.05)。最终进入Cox回归模型的变量为肿瘤分化程度(P=0.003,风险比=2.202)。结论动脉微泵灌注奥沙利铂方案TACE治疗结直肠癌术后肝转移疗效确切,具有较高的客观有效率。     

结,直肠癌肝转移的外科治疗

对６８例结、直肠癌肝转移患者中的１３例行手术治疗。作者认为：把握手术时机和适应证，提高手术切除成功率是提高存活率的关键。     

同期肝切除治疗结直肠癌同时性肝转移

目的探讨结直肠癌同时性肝转移肝肠同期手术的疗效。方法回顾性分析1994年8月至2004年12月在我院行外科手术治疗的121例同时性结直肠癌肝转移患者的临床资料。结果在121例同时性结直肠癌肝转移患者中,99例行结直肠癌根治性切除术,剔除2例行原位肝移植患者后,同期肝切除组41例（A组）,对肝转移瘤行姑息外科治疗组56例（B组）,即转移瘤未能完全经手术切除者,A、B组患者性别、年龄、原发瘤部位、浸润深度、淋巴结转移等差异均无统计学意义,肝转移瘤数目（x^2=40.41,P＜0.05）、肝转移瘤分布（x^2=11.61,P＜0.05）差异有统计学意义;两组患者中位生存期分别为28.9个月、17.1个月,5年生存率分别为14％、0,其中A组患者中位无瘤生存期为19.5个月,1、3、5年生存率为93%、44%和14%。结论同期肝切除能为部分结直肠癌同时性肝转移患者提供治愈机会,对于合适的患者应力争行同期肝切除术。     

经动脉选择性内放射治疗用于结直肠癌肝转移研究进展

肝脏是结直肠癌最常见转移部位,结直肠癌肝转移(CRLM)是导致患者死亡的主要原因之一。选择性内放射治疗(SIRT)的有效性及安全性已得到证实。本文对SIRT用于CRLM的临床研究进展进行综述。     

结直肠癌肝转移的外科治疗

目的探讨结直肠癌肝转移的手术疗效。方法1996年8月～2000年8月手术治疗结直肠癌肝转移患者31例,行原发癌与转移癌同时切除者9例,结直肠癌根治术后6月再切除肝转移灶者18例;切除肝转移灶后2月再切除原发病灶者4例。原发灶行右半结肠切除5例,横结肠切除4例,左半结肠切除7例,Dixon术12例,Miles术3例。肝转移灶行左外叶切除5例,左半肝切除2例,右后叶切除4例,右前叶切除2例,左或右肝不规则切除18例。结果全组无手术死亡。术后粘连性肠梗阻1例,切口感染3例,经对症治疗后均痊愈出院。平均随访6.4(0.5～8)年,1、2、5年生存率分别为100%、80.6%、29.0%。同期手术者与分期手术者5年生存率分别为33.3%和27.3%,无统计学差异(P>0.05)。结论对结直肠癌肝转移患者应积极争取手术切除,术后可配合其他综合治疗;对原发灶早期诊断、早期手术治疗及辅助化疗有利于防止结直肠癌肝转移。     

结直肠癌肝转移的综合治疗

结直肠癌肝转移是影响结直肠癌预后的重要因素,治疗方案包括手术治疗、化疗(全身静脉化疗和介入治疗)、基因治疗和局部治疗(射频消融、激光消融、无水酒精注射和冷冻切除术)等,其中手术是目前唯一有效的治愈手段,手术死亡率为1%~2.8%,术后5年生存率为34%~38%,但仅有10%~25%结直肠癌肝转移患者确诊时适于手术切除,因此各种非手术治疗的作用正日益受到关注。本文就结直肠癌肝转移的综合治疗作一综述。     

结直肠癌肝转移的外科治疗

目的　探讨结、直肠癌肝转移的外科治疗。方法　对１９９３ 年１ 月至１９９９ 年１ 月的１９ 例结、直肠癌肝转移患者行外科治疗。其中６ 例同期切除,１０ 例分期切除,１ 例肝动脉结扎加无水乙醇注射,２ 例通过肝动脉结扎加化学药物治疗（化疗） 泵灌注化疗而获得二期手术切除机会。手术方式行肝不规则楔形切除１６ 例,左半肝切除２ 例。结果　术后１、３、５ 年生存率分别为８９％ 、５８％ 、２１％ 。６ 例同期肝切除者平均生存期２３ 个月,１０ 例分期肝切除者的平均生存期为３２ 个月。结论　掌握手术时机和适应证,积极进行肝动脉灌注化疗,提高手术切除成功率是提高存活率的关键。     

结直肠癌肝转移的外科治疗

目的探讨结直肠癌肝转移的外科手术适应证和疗效,以及临床病理因素对其预后的影响。方法回顾性分析1991年1月至2000年12月间施行肝切除术的61例结直肠癌肝转移患者的临床资料。结果结直肠癌肝转移切除术后1、3、5年生存率分别为72.1%、58.1%和26.0%,术后出现并发症8例,20例肝转移灶有假包膜形成。结直肠癌Dukes分期、病理类型、转移灶数目、假包膜形成对术后生存率有影响(P<0.05)。术后综合治疗者3年生存率明显优于无综合治疗者(P<0.05)。肝转移灶大小及其切除时间并不影响患者预后(P>0.05)。结论临床病理分期早、肿瘤分化程度高、转移灶数目不超过3个、肿瘤假包膜形成及术后综合治疗预示结直肠癌肝转移切除患者有较好的预后。     

手术切除结直肠癌肝多个转移瘤的效果分析

目的对于结直肠癌患者肝内存在多个转移瘤,手术切除的价值存在争议,本文旨在研究手术切除大肠癌肝多个ΚΣ瘤的效果。方法回顾性分析1996年1月至2006年12月收治的经手术切除的结直肠癌肝转移瘤患者60例,比较肝内单个转移瘤(35例)与多个转移瘤(25例)患者临床和预后资料。结果两组均无手术死亡。多个转移瘤组和单个转移瘤组相比,手术并发症为12.0%vs11.4%(P=1.000);平均住院时间为(14.9±5.1)dvs(15.7±5.8)d(P=0.844);中位生存期为28个月vs35个月(P=0.089);中位无瘤生存期为16个月vs19个月(P=0.112);肝内复发率为72.0%vs51.5%(P=0.109)。多个转移瘤组3、5年总生存率分别是48.4%、30.8%,单个转移瘤组分别为68.6%、57.7%(P=0.165)。结论手术切除结直肠癌肝脏多个转移瘤可取得与单个转移瘤相似的效果。手术切除不应视为肝多个转移瘤的禁忌证。术后辅以全身化疗常可以改善预后。     

术中瘤内置管后装放疗治疗转移性肝癌

目的 观察转移性肝癌组织间插植后装放疗的效果、毒副反应，探讨其应用于治疗结、直肠癌术后肝转移的可行性。方法 1992年11月至1997年5月对18例结、直肠癌术后确诊肝转移病人行剖腹探查术中瘤内置管组织间插植后装放疗。放射源为高剂量率^192Ir，每次照射8－10Gy，总量30－40Gy，1－2周内完成。结果 18例无明显毒副反应，中位生存期25.6个月，1，3，5年生存率（按寿命表法）分别为71.6%,28.7%,7.2%。CEA滴度变化可做为肿瘤控制与否及有无肝内外隐匿病灶的重要指标。结论 术中、肝穿刺置管法安全、可靠；作为局部根治性治疗手段，对原发于结、直肠的肝转移癌的治疗是有效的。但其能否与手术切除效果相当尚需进一步观察。     

Combination of hepatic arterial infusion and systemic chemotherapy for gastric cancer with synchronous hepatic metastases

Between 1964 and 1981, seventy-two Japanese patients with gastric cancer associated with hepatic metastases, in whom the primary tumor had been resected, were treated in a nonrandomized manner at the Second Department of Surgery, Kyushu University Hospital. Fourteen received hepatic arterial infusion (HAI) of 5-FU and Mitomycin C (MMC) combined with systemic chemotherapy, 26 combination systemic chemotherapy of MMC, Futraful and PSK, 18 single drug (MMC) therapy, and 14 no chemotherapy. The average survival was 264 days in HAI combined with systemic chemotherapy, 208 in the combination systemic chemotherapy, 156 in the single drug therapy and 135 in those given no chemotherapy. One year survival and nine month survival rates were 21.4 per cent and 42.9 per cent in HAI combined with systemic chemotherapy, 11.5 per cent and 19.2 per cent in the combination systemic chemotherapy, 5.6 per cent and 11.1 per cent in the single drug therapy and 7.1 per cent and 14.3 per cent in the no chemotherapy group, respectively (HAI vs single drug therapy and no chemotherapy, p<0.01). Five of 14 patients treated with HAI combined with systemic chemotherapy showed a partial response (>50 per cent reduction in tumor size), and the average survival time was 335 days, while that of nonresponders was 224 days. Six of 14 patients treated with combination infusion therapy with MMC and 5-FU survived 314 days, as compared to 201 days for patients with infusion of 5-FU alone.     

改良FOLFOXIRI方案在晚期结直肠癌患者一线治疗中的安全性和疗效分析

目的 观察降低剂量的氟尿嘧啶联合奥沙利铂、伊立替康组成的改良FOLFOXIRI方案一线治疗晚期结直肠癌的安全性和有效性.方法 对中山大学附属第六医院2010年1月至2014年1月间连续收治的53例晚期结直肠癌患者采用改良FOLFOXIRI化疗方案进行治疗,其中11例联合了靶向药物治疗.按照常见不良反应分级标准（CTCAE）3.0版行安全性评价;按照实体瘤的疗效评价标准（RECIST） 1.1版进行疗效评价;采用双脱氧链终止测序法进行Kras和Braf基因检测,评估两种基因与疗效的关系.结果 全组53例患者在治疗期间,未出现治疗相关性死亡,Ⅲ～Ⅳ级不良反应发生率为32.1％（17/53）,其中粒细胞下降发生率为13.2％（7/53）,贫血发生率为11.3％（6/53）,疲乏发生率为9.4％（5/53）.44例患者获疗效评价,客观缓解率（ORR）和疾病控制率（DCR）分别为65.9％（29/44）和90.9％（40/44）,R0切除率为29.5％（13/44）.三药联合靶向药物治疗者ORR为72.7％（8/11）,较单纯三药治疗患者（63.6％,21/33）有所提高,但差异无统计学意义（P=0.435）.48例结直肠癌组织石蜡标本检测中发现,发生Kras突变者21例（43.75％）,Braf突变者3例（6.25％）.两种基因突变型与野生型患者的ORR和DCR的差异均无统计学意义（均P＞0.05）.结论 改良FOLFOXIRI方案对晚期结直肠癌的治疗近期疗效较为满意,治疗的耐受性和安全性较好。     

肝转移癌的造影表现及肝动脉灌注化疗并栓塞治疗疗效观察

目的 观察肝转移癌的造影表现及肝动脉灌注化疗栓塞治疗肝转移癌的疗效。方法 总结分析行TACE治疗的67例肝转移癌的造影表现及疗效,全部病例均经2次以上TACE或TAC治疗,共230次。灌注化疗加栓塞58例,占87％。结果 单发转移3例,多发转移61例,弥漫转移3例;多血供型24例,少血供型43例;总有效率87％,显有效率52％。结论 TACE目前是治疗肝转移癌尤其是多发肝转移癌的首选方法,但其疗效有待于进一步提高。     

结直肠癌肝转移根治性切除预后因素分析

目的 分析影响结直肠癌肝转移患者根治性手术切除预后的临床病理因素,探讨改善患者预后的方法.方法 收集2005年1月至201 1年12月江苏省苏北人民医院和复旦大学附属肿瘤医院收治的103例结直肠癌肝转移根治性切除患者的临床资料.采用Kaplan-Meier法计算生存率,用Log-rank法分析患者生存情况,对各种影响预后的因素分别进行单变量和多变量Cox回归分析.结果 103例患者均获随访,随访时间10～ 60个月,术后1、3、5年生存率分别为90％、49％、39％.单因素分析结果显示:肝转移灶数目、大小、分布、术前CEA水平、手术并发症、术后化疗是肝转移灶切除术后的影响因素(x2值分别为24.732、9.461、9.568、25.948、25.370、5.701,P＜0.05);多因素分析显示,肝转移灶数目、肝转移灶切除术前CEA水平、手术并发症是影响预后的独立因素(Wald=7.974、12.051、11.547,P＜0.05).结论 肝转移灶数目、肝转移灶切除术前CEA水平和手术并发症是影响结直肠癌肝转移患者预后的独立因素.适当扩大手术切除的适应证,加强对高危患者的随访和术后辅助化疗,可能改善肝转移患者的预后.     

Safety and efficacy of hepatic vein reconstruction for colorectal liver metastases

Background

Colorectal liver metastases with hepatic vein (HV) involvement may require combined resection of the liver and HV. However, the short- and long-term outcomes of such a procedure remain unclear.

Methods

We reviewed 16 cases of liver resection with major HV resection and reconstruction.

Results

The patients had a median age of 58.5 years (range, 50–74 y). In total, 18 HVs were reconstructed using a customized great saphenous vein graft (n = 10), direct anastomosis (n = 1), external iliac vein (n = 2), portal vein (n = 1), umbilical vein patch graft (n = 3), or ovarian vein patch graft (n = 1). There was no hospital mortality, and the morbidity rate was 50%. With a median follow-up period of 30 months (range, 4–89 mo), 3 patients died of tumor recurrence and 13 were alive with (n = 6) and without (n = 7) disease. Cumulative 1-, 3-, and 5-year survival rates were 93%, 76%, and 76%, respectively.

Conclusions

HV resection and reconstruction combined with liver resection can be performed safely with reasonable long-term results.