经肝动脉灌注奥沙利铂联合卡培他滨治疗结肠癌肝转移

目的探讨经肝动脉灌注奥沙利铂联合卡培他滨治疗结肠癌肝转移的有效性及安全性。方法回顾性分析50例结肠癌肝转移患者的资料,对其中22例采用经肝动脉灌注奥沙利铂联合卡培他滨治疗(A组),28例采用静脉滴注奥沙利铂联合卡培他滨治疗(B组),分析并比较2组患者的疗效及不良反应发生情况。采用Kaplan-Meier法进行生存分析,以Log-rank检验比较2组患者无进展生存期(PFS)的差异,以Cox模型分析其影响因素。结果治疗结束后2组患者血清癌胚抗原(CEA)均较治疗前减低(P均0.001),但组间差异无统计学意义(t=1.059,P=0.295)。A组和B组治疗开始后6个月客观缓解率(ORR)分别为59.09%(13/22)、35.71%(10/28),中位PFS分别为10.0、6.5个月(P均0.05);A组周围神经毒性发生率低于B组(χ~2=4.266,P=0.039)。结肠癌原发灶病理类型、肝转移灶数目、奥沙利铂给药方式为PFS的独立影响因素(P均0.05)。结论对结肠癌肝转移患者行肝动脉灌注奥沙利铂联合卡培他滨治疗效果确切,有利于延长PFS并减少不良反应。     

肝动脉灌注化疗联合XELOX方案治疗胃肠道恶性肿瘤肝转移的疗效及安全性分析

目的探讨肝动脉灌注化疗(hepatic artery infusion chemotherapy,HAIC)联合XELOX方案对胃肠道恶性肿瘤肝转移的疗效和安全性。方法回顾性分析我院2002年1月~2008年12月不可切除的胃肠道恶性肿瘤肝转移41例资料,肝动脉灌注氟尿嘧啶脱氧核苷(fluorodeoxyuridine,FUDR)500 mg,第1~5天,静脉给予奥沙利铂130 mg/m2,第1天,口服卡培他滨1000 mg/m2,每天2次,第1~14天。18例为一线化疗,17例为二线化疗,6例为三/四线化疗。观察无进展生存期(progression-free survival,PFS)、有效率(response rate RR)及总生存期(overall survival,OS),并评估药物不良反应。结果一线化疗18例RR 44.4%(8/18),肝脏转移灶RR 50.0%(9/18);二线化疗17例RR 23.5%(4/17),肝脏转移灶RR 29.4%(5/17)。一线、二线及三/四线治疗的总体中位PFS分别为8、4、2.5月,肝转移灶中位PFS分别为10.5、5、4月。Ⅲ/Ⅳ度不良反应主要以白细胞减少(4例)、手足综合征(4例)、感觉神经障碍(3例)、腹泻(4例)为主,均对症治疗治愈。结论 HAIC联合XELOX方案治疗合并肝转移的晚期胃肠道恶性肿瘤有一定疗效,一线治疗生存获益更明显,不良反应可耐受。     

奥沙利铂或伊立替康联合氟尿嘧啶在KRAS突变型的晚期结直肠癌一线化疗中的疗效比较

【摘要】〓目的〓有研究认为KRAS突变型晚期结直肠癌对奥沙利铂较为敏感,本文在前期研究的基础上扩大样本量,探讨KRAS突变型患者一线以奥沙利铂为基础化疗方案是否优于伊立替康为基础化疗方案。方法〓回顾分析2005年4月~2016年6月期间5个中心、经病理和基因检测确诊的112例KRAS基因突变型晚期结直肠癌患者,一线接受奥沙利铂为基础化疗方案72例,伊立替康为基础方案40例,主要观察终点指标OS,次要终点指标为DCR、PFS。结果〓奥沙利铂组与伊立替康组的中位OS分别为24.9个月和26.5个月(P=0.978)、DCR分别为69.4%和62.5%(χ2=0.561,P=0.454)、中位PFS分别为8.5个月和8.5个月(P=0.412),两组差别均无统计学意义。 结论〓KRAS基因突变型晚期结直肠癌患者,一线应用奥沙利铂与伊立替康为基础化疗方案相比疗效无差异。     

结直肠癌肝转移一期联合手术化疗的临床研究

目的探讨结直肠癌肝转移一期联合手术辅助化疗的有效途径及临床价值.方法回顾性分析一期联合手术切除原发癌及转移癌,经肝动脉门静脉双置泵栓塞灌注化疗,肿瘤局部注射无水酒精及热电疗法综合性治疗结直肠癌肝转移36例的临床资料.结果本组36例结直肠癌患者原发癌均获切除,其中一期切除肝转移癌17例,6例复发,4例再次手术切除.19例不能切除的转移性肝癌,行肝动脉门静脉双置泵栓塞灌注化疗,无水酒精注射和热电疗法.肿瘤直径平均缩小57%,其中4例因肿瘤缩小行二期手术切除.1、2、3年生存率分别为切除组94%,82%,65%;明显高于置泵组的74%,53%,32%(P<0.01).结论结直肠癌肝转移一期联合手术切除加肝动脉门静脉双置泵栓塞灌注化疗,是一种首选而有效的治疗方法.不能切除肝转移癌者,只要切除原发肿瘤,肝动脉门静脉置泵栓塞灌注化疗,可明显延长病人生存期,改善预后.     

直肠癌根治术后髂内动脉加门静脉置泵化疗预防局部复发和肝转移的研究

目的探讨髂内动脉加门静脉置泵化疗预防直肠癌术后局部复发和肝转移的价值.方法将我院96例直肠癌术前随机分成两组,门静脉加髂内动脉灌注化疗组(治疗组)48例与外周静脉化疗组(对照组)48例,对其疗效进行分析.结果治疗组1、3、5年生存率分别是100%、83%、52%;局部复发率和肝转移率是13%、13%.对照组是88%、68%、32%,26%、28%.两组各项指标分别比较,差异有显著意义(P<0.01).结论置泵灌注化疗在预防直肠癌术后局部复发和肝脏转移的治疗效果优于外周静脉全身化疗.     

结直肠癌同时性肝转移治疗46例分析

目的:探讨结直肠癌同时性肝转移的有效治疗方法。方法:对1996～2004年收治的46例结直肠癌同时性肝转移的临床资料和随访资料进行回顾性分析。根据治疗方法的不同分为3组:A组21例,为一期切除原发灶和肝转移灶并经肝动脉和门静脉置泵化疗者;B组15例,为单纯原发灶切除并经肝动脉和门静脉置泵化疗者;C组10例,为原发灶和肝转移灶均未能切除而仅行肝动脉和门静脉置泵化疗者。用KaplanMeier法对病人的生存时间作统计分析。结果:A、B、C3组术后中位生存期分别为38、20和13个月;各组之间术后生存时间的比较均有显著统计学差异(P<0.01)。结论:结直肠癌原发灶和肝转移灶一期手术切除并经肝动脉和门静脉置泵化疗的疗效最好;肝转移灶无法切除者能将原发灶切除并经肝动脉和门静脉置泵化疗也可取得较好的疗效;原发灶和肝转移灶未能切除而仅经肝动脉和门静脉置泵化疗的疗效相对较差。对结直肠癌同时性肝转移应采取以手术切除为主的综合措施进行积极治疗。     

射频消融、TACE及联合治疗结直肠癌肝转移的效果比较

目的比较肝动脉栓塞化疗(TACE)、射频消融(RFA)及联合治疗结直肠癌肝转移的效果。方法将120例结直肠癌肝转移患者为3组,每组40例。TACE组给予TACE,RFA组行RFA治疗,联合组在TACE4周后给予RFA治疗。比较3组疗效。随访3 a观察患者生存情况。结果 TACE组与RFA组的有效率差异无统计学意义(P0.05)。联合组较其余2组有效率均明显提高,差异有统计学意义(P0.05)。治疗1 a后,3组患者生存率差异无统计学意义(P0.05)。治疗2、3 a后,联合组较其余2组生存率明显升高,差异有统计学意义(P0.05)。结论 RFA联合TACE治疗结直肠癌肝转移,疗效优于单一TACE治疗或RFA治疗,并明显改善患者术后的生存质量。     

以经导管动脉化疗栓塞为基础的联合治疗方案在不可切除的结直肠癌肝转移中应用的新进展

目的了解以经导管动脉化疗栓塞(TACE)为基础联合全身化疗、分子靶向治疗、门静脉栓塞、射频消融等多种治疗方案对不可切除的结直肠癌肝转移患者进行治疗的新进展,探索适用于晚期结直肠癌肝转移患者安全、有效的联合治疗方法,从而控制疾病快速进展,改善患者生存质量。方法收集国内外有关以TACE为主导的联合治疗方案应用于结直肠癌肝转移外科治疗新进展的文献,就联合方案应用于结直肠癌肝转移治疗的新进展以及各联合治疗方案的优势与特点进行综述。结果对于晚期原发或继发性肝脏恶性肿瘤,TACE是一种安全、有效的治疗方法,在此基础上联合其他治疗方案与单一的治疗方案相比,在提高患者生活质量、延长生存时间这两方面均具有明显优势。随着各种新的治疗药物的不断涌现,多种介入治疗方式的快速发展,都为改善结直肠癌肝转移患者的远期生存带来利好因素。结论我们应该加强对不可手术切除的结直肠癌肝转移综合治疗的重视,提高对晚期肿瘤个体化治疗的认识,积极推动联合治疗方案在结直肠癌肝转移治疗中的应用。     

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

目的 比较FOLFOX-6方案全身化疗与传统以氟尿嘧啶为主的肝动脉灌注化疗对结直肠癌术后肝转移病人的疗效并分析影响结直肠癌术后肝转移病人的预后因素.方法 46名结直肠癌术后肝转移病人随机分配到全身化疗组(实验组)和介入治疗组(对照组),对比观察近远期疗效、毒副作用和生活质量.将影响预后的临床特征和治疗方式进行单因素和多因素分析.结果 实验组、对照组总生存率差异有统计学意义(P=0.048),中位生存时间分别为15.0个月和11.2个月(P＜0.05);治疗总有效率两组差异有统计学意义(50%和10%;P=0.011);两组治疗期间的PS评分差异无统计学意义(P=0.126).毒副作用除骨髓抑制、腹痛外,其它比较差异均无统计学意义.单因素分析显示,原发病灶是否浸润浆膜、肝转移灶分布、肝转移病灶最大直径、肝转移灶数目、原发癌有无淋巴结转移以及治疗方式与预后相关.多因素分析后发现,肝转移灶最大直径、肝转移病灶数目、原发癌灶是否浸透浆膜层和治疗模式为影响预后的独立因素.结论 以草酸铂为主的FOLFOX-6方案比传统的以氟尿嘧啶为主的肝动脉灌注化疗有更好的治疗缓解率和远期疗效;肝转移灶最大直径＞5 cm、肝转移灶多发和原发病灶浸透浆膜层提示病人预后不良,采取以草酸铂为主的全身化疗,预后更好.传统药物介人治疗需要改进,局部介入与全身治疗结合的方式值得进一步探究.     

预后营养指数对结直肠癌同时性肝转移患者预后评估的价值

目的探讨治疗前预后营养指数(PNI)与结直肠癌同时性肝转移患者预后的关系。方法回顾性分析2015年1月至2017年1月深圳市人民医院初诊初治的结直肠癌同时性肝转移患者83例临床资料,记录患者5年随访生存结局,利用ROC曲线选取约登指数最大值时的PNI值为截断值,分为高PNI组和低PNI组。采用Kaplan-Meier法进行生存分析,Cox比例风险模型筛选影响患者预后的因素。结果 83例中位随访时间13(9～25)个月,44例死亡。ROC曲线选取PNI值为50.4,约登指数为1.31,分为低PNI组44例(PNI50.4,53.01%),高PNI组39例(PNI≥50.4,46.99%)。低PNI组的OS、PFS较高PNI组明显缩短(P=0.005、0.018)。PNI50.4、未行根治手术、肝多发转移、年龄≥60岁是OS的独立预后不良因素,PNI50.4、未行根治手术是PFS独立预后不良因素(均P0.05)。结论治疗前PNI是结直肠癌同时性肝转移患者OS和PFS的独立预测因子。     

125I粒子植入联合化学治疗干预晚期结直肠癌肝转移瘤效果

目的 观察¹²⁵I粒子植入联合化学治疗（简称化疗）对晚期结直肠癌肝转移瘤的治疗效果及安全性。方法 对27例晚期结直肠癌肝转移瘤（60个病灶）患者的肝转移瘤病灶行放射性¹²⁵I粒子植入,术后行二线化疗,观察治疗效果、不良反应及预后。结果 60个病灶均顺利植入粒子,剂量分布均匀,共植入粒子1 995枚,平均每个病灶植入粒子（33.41±24.79）枚。术后不良反应轻,予对症处理后均恢复。术后1周肝功能与术前相比无明显差异。以奥沙利铂联合方案化疗6例,伊立替康联合方案21例。化疗3、6个周期后肝转移瘤病灶直径及癌胚抗原（CEA）水平均较术前显著降低（P均<0.001）。中位无进展生存期为8.1个月,中位总生存期为14.6个月。结论 ¹²⁵I粒子植入联合化疗对晚期结直肠癌肝转移瘤安全性好,近期疗效佳。     

TACE联合射频消融治疗累及第二肝门区肝细胞癌的效果

目的观察TACE联合射频消融(RFA)治疗累及第二肝门区肝细胞癌(HCC)的效果。方法收集41例HCC患者,共44个肿瘤累及第二肝门区,于TACE后行RFA治疗。采用Kaplan-Meier法绘制生存曲线,统计患者中位总生存期(OS)及中位无进展生存期(PFS)。结果第二肝门区HCC完全消融率为81.82%(36/44)。消融后17例出现疼痛、10例一过性肝功能损伤、9例发热、2例气胸、1例胸腔积液、1例出血,均经对症处理后痊愈;无死亡病例。41例患者术后中位OS为28个月,中位PFS为10个月。结论 TACE联合RFA可有效治疗累及第二肝门区的HCC,且并发症少,患者预后较好。     

A Real-World,Population-Based Analysis of the Outcomes of Colorectal Cancer Patients with Isolated Synchronous Liver or Lung Metastases Treated with Metastasectomy

Objective

To assess the survival outcomes among a contemporary cohort of colorectal cancer patients with isolated synchronous liver or lung metastases treated with or without surgical resection of the metastases.

Methods

Surveillance, epidemiology and end results database has been accessed and cases with isolated liver or lung metastases diagnosed 2010–2015 have been accessed. Kaplan–Meier survival estimates were used to compare overall survival among patients who had or had not undergone metastasectomy. Multivariable Cox regression analysis was then used to assess the impact of metastasectomy on colorectal cancer-specific survival.

Results

A total of 16,372 patients with colorectal cancer with isolated liver or lung metastases (M1a disease) were included in the current analysis (including 14,832 patients with isolated liver metastases and 1540 patients with isolated lung metastases). Patients who had undergone surgical resection of liver metastases have better overall survival compared to patients who had not undergone surgical resection of liver metastases (median overall survival: 38.0 months vs. 13.0 months; P < 0.001). Likewise, patients who had undergone surgical resection of lung metastases have better overall survival compared to patients who had not undergone surgical resection of lung metastases (median overall survival: 45.0 months vs. 19.0 months; P < 0.001). In a multivariable Cox regression analysis and among patients with isolated liver metastases, surgery to the metastases was associated with a reduced hazard of death (hazard ratio (HR) 0.567; 95% CI 0.529–0.609; P < 0.001). Likewise, and among patients with isolated lung metastases, surgery to the metastases was associated with a reduced hazard of death (HR 0.482; 95% CI 0.349–0.665; P < 0.001).

Conclusion

In a contemporary cohort, metastasectomy seems to be associated with improvement in overall and cancer-specific survival among patients with isolated synchronous liver or lung metastases from colorectal cancer. Whether this survival difference is totally ascribed to the effect of metastasectomy or it is the fact that patients who were eligible for surgical resection have limited disease extent and better medical profile (thus, leading to better survival) is unclear from such a population-based study.

     

结直肠癌同时性肝转移新辅助化疗后手术对比直接手术患者的生存疗效

目的:对比结直肠癌同时性肝转移行新辅助化疗后手术与直接手术患者的生存疗效。方法:本研究采用回顾性队列研究方法,纳入在2008年1月至2018年12月期间,北京大学肿瘤医院肝胆胰外一科收治的282例初始评估为技术上可切除的结直肠同时性肝转移患者。以肝转移术前是否接受过新辅助化疗,分为新辅助化疗组（244例）和直接手术组（...     

结直肠癌肝转移合并同时性肺转移患者手术治疗疗效分析

背景与目的：对于结直肠癌肝转移合并可切除肺转移的患者,手术治疗的疗效已经得到广泛认可,但对于合并不可切除的肺转移患者的治疗策略仍需要进一步明确。因此,本研究通过对笔者单位收治的结直肠癌肝转移合并同时性肺转移患者临床资料的回顾性分析,以期为该类患者的治疗提供数据参考。方法：本研究采用回顾性队列研究方法,纳入2008年1月—2020年12月期间在北京大学肿瘤医院肝胆胰外一科行手术治疗的127例结直肠癌肝转移合并同时性肺转移患者的资料,所有患者原发灶及肝转移灶均按肿瘤根治原则行完整切除（R0/R1）,其中31例行肺转移灶的根治性局部治疗（局部治疗组）,96例肺转移灶未行局部治疗（非局部治疗组）,比较两组患者的临床资料、总生存时间（OS）、无复发生存时间（RFS）,并对非局部治疗组的患者进行预后相关因素分析。结果：除局部治疗组肺转移灶直径大于非局部治疗组外（P<0.05）,两组其余一般临床资料均无明显差异（均P>0.05）。全组患者中位随访时间为30 (5～134)个月,失访率3%。全组患者中位OS为41 (4～118)个月,1、3年OS率分别为96.8%和59.7%,其中非局部治...     

Preoperative Chemotherapy and the Outcome of Liver Resection for Colorectal Metastases

Background Neoadjuvant systemic chemotherapy is being increasingly used prior to liver resection for colorectal metastases. Oxaliplatin has been implicated in causing structural changes to the liver parenchyma, and such changes may increase the morbidity and mortality of surgery. Patients and Methods A retrospective study was undertaken of 101 consecutive patients who had undergone liver resection for colorectal metastases in two HPB centers. Preoperative demographic and premorbid data were gathered along with liver function tests and tumor markers. A subjective assessment of the surgical procedure was noted, and in-hospital morbidity and mortality were calculated. The effect of preoperative chemotherapy on short-term and long-term outcome was analyzed, and actuarial 1 and 3 year survival was determined. Results Patients who received neoadjuvant chemotherapy had a higher number of metastases (median 2, range 1–8 versus median 1, range 1–5; P = 0.019) and more had synchronous tumors (24 patients versus 8; P < 0.001). Overall morbidity was 37% and hospital mortality was 3.9%. Operative and in-hospital outcome was not influenced by chemotherapy. Long-term survival was worse in patients who had received preoperative chemotherapy (actuarial 3-year survival 62% versus 80%; P = 0.04). Conclusions This study shows no evidence that neoadjuvant chemotherapy, and in particular oxaliplatin, increases the risk associated with liver resection for colorectal metastases. Long-term outcome is reduced in patients receiving preoperative chemotherapy, although they have more advanced disease.     

Resecting large numbers of hepatic colorectal metastases

Background : Despite the widespread use of surgical resection as a treatment for hepatic colorectal metastases, the value of resecting more than three metastases remains controversial. It was the objective of this study to determine if resection of larger numbers of metastases affects patient survival. Method : The survival of 123 consecutive patients who underwent curative hepatic resection for colorectal metastases between 1989 and 1999 by a single surgeon was analysed retrospectively. Kaplan–Meier survival statistics and Cox regression were used to determine the factors that affected survival, and logistic regression was used to determine the factors that affected the risk of recurrence of hepatic disease. Results : The median survival rate for the whole group of patients was 38 months, with 1, 3 and 5 year survival rates of 88%, 53% and 31% respectively. The survival rate of patients undergoing resection of four to seven metastases (n = 22; 5 year survival = 39%) was not significantly different to that of patients undergoing resection of one to three metastases (n = 91; 5 year survival = 30%), P = 0.9. Age, sex, primary cancer site, hepatic disease distribution, resection margins and adjuvant hepatic arterial chemotherapy (HAC) did not affect survival. Local invasion of the hepatic metastases (relative risk (RR) = 2.9; P = 0.001) and hepatic disease recurrence (RR = 2.1; P = 0.007) were the only factors that independently affected survival. Local invasion of the hepatic metastasis was the only factor associated with an increased risk of hepatic recurrence (RR = 2.8; P = 0.03). Adjuvant HAC did not affect the risk of hepatic recurrence (RR = 1.5, P = 0.4). Conclusion : Although there are no randomized trials that quantify any survival benefit from resection of liver metastases, the comparison of our results with well documented historical evidence indicates that surgical resection of up to seven colorectal liver metastases can result in a significant survival benefit.     

对比雷替曲塞与氟尿嘧啶TACE治疗中晚期原发性肝癌疗效及安全性:Meta分析

目的通过Meta分析对比采用雷替曲塞与氟尿嘧啶行TACE治疗中晚期原发性肝癌的疗效及安全性。方法结合计算机及人工检索PubMed、Cochrane Library、Web of Science、中国生物医学文献数据库、万方数据库及中国知网收录的有关对比分析雷替曲塞与氟尿嘧啶TACE治疗中晚期原发性肝癌的文献,并从中提取相关资料。通过Meta分析方法对2种TACE的客观有效率(ORR)、疾病控制率(DCR)、患者总生存率(OS)及术后不良反应进行评价。结果最终8篇文献、共635例患者纳入分析。雷替曲塞TACE的ORR[相对危险度(RR)=1.25,95%CI(1.06,1.47),P=0.008]及DCR[RR=1.17,95%CI(1.08,1.26),P0.001]均高于氟尿嘧啶TACE,期间患者OS[RR=1.15,95%CI(0.95,1.39),P=0.141]及术后不良反应[恶心、呕吐:RR=0.90,95%CI(0.73,1.11),P=0.339;发热:RR=0.90,95%CI(0.77,1.06),P=0.219;肝区疼痛:RR=0.90,95%CI(0.80,1.01),P=0.219;外周血白细胞减少:RR=0.89,95%CI(0.65,1.21),P=0.462;转氨酶升高:RR=0.96,95%CI(0.80,1.16),P=0.663]差异均无统计学意义。结论 TACE治疗中晚期原发性肝癌时,采用雷替曲塞较氟尿嘧啶疗效更优,安全性则相似。     

The Landmark Series: Surgical Treatment of Colorectal Cancer Peritoneal Metastases

Background

Peritoneal metastases (PM) are a form of metastatic spread affecting approximately 5-15% of colon cancer patients. The attitude towards management of peritoneal metastases has evolved from therapeutic nihilism towards a more comprehensive and multidisciplinary approach, in large part due to the development of cytoreductive surgery (CRS), usually coupled with heated intraperitoneal chemotherapy (HIPEC), along with the constant improvement of systemic chemotherapy of colorectal cancer. Several landmark studies, including 5 randomized controlled trials have marked the development and refinement of surgical approaches to treating colorectal cancer peritoneal metastases.

Methods

This review article focuses on these landmark studies and their influence in 4 key areas: the evidence supporting surgical resection of peritoneal metastases, the identification and standardization of important prognostic variables influencing patient selection, the role of surgery and intraperitoneal chemotherapy in prevention of colorectal PM and the role of intraperitoneal chemotherapy as an adjuvant to surgical resection.

Results

These landmark studies indicate that surgical resection of colorectal PM should be considered as a therapeutic option in appropriately selected patients and when adequate surgical expertise is available. Standardized prognostic variables including the Peritoneal Cancer Index and the Completeness of Cytoreduction Score should be used for evaluating both indications and outcomes.

Conclusions

Current evidence does not support the use of second look surgery with oxaliplatin HIPEC or prophylactic oxaliplatin HIPEC in patients with high risk colon cancer nor the use of oxaliplatin HIPEC with CRS of colorectal PM.