超声造影定量分析在结直肠癌肝转移化疗早期疗效评价中的应用价值

目的:探讨超声造影(CEUS)定量分析在结直肠癌肝转移化疗早期疗效评价中的应用价值.方法:选取2018年10月至2020年10月于本院行化疗治疗的56例结直肠癌肝转移患者为研究对象,随机分为2组,各28例,一组采用m FO L-FOX6方案化疗(单一治疗组),另一组在mFOLFOX6方案化疗基础上联合应用贝伐单抗(联合...     

贝伐珠单抗联合化疗治疗进展期结直肠癌的疗效观察

目的:观察贝伐珠单抗联合化疗治疗进展期结直肠癌患者的疗效.方法:将进展期结直肠癌患者92例随机分为贝伐珠单抗组和对照组,每组46例.贝伐珠单抗组患者采用贝伐珠单抗加化疗治疗,对照组患者采用常规化疗,观察2组患者的疗效、血清指标、无进展生存情况及术后不良反应发生率.结果:贝伐珠单抗组总有效率及1年、2年、3年无进展生存率...     

应用超声造影评价结直肠癌抗血管治疗早期效果的可行性研究

目的探讨应用超声造影评价结直肠癌患者抗血管靶向治疗早期效果的价值。方法回顾性分析本院收治的80例结直肠癌患者的临床资料,所有患者均为经抗血管靶向药物(FOLFOX+贝伐单抗方案)治疗6个周期,2周为1个周期,治疗结束后按照改良实体瘤疗效评价标准(m RECIST标准)分为有效组58例与无效组22例,所有患者在治疗前、治疗2个周期后经超声造影检查,利用超声造影定量分析软件得出四个血流灌注参数,分别为峰值强度(PI)、达峰时间(TTP)、曲线下面积(AUC)、上升斜率(Pw),记录两组定量参数,分析治疗前、治疗2个周期后定量参数变化百分数,从而判断治疗效果。结果两组抗血管治疗前后PI、TTP、AUC比较均无统计学意义(均P0.05)。治疗前有效组Pw显著高于无效组(P0.05),治疗2个周期后两组差异无统计学意义(P0.05)。两组治疗前后PI及Pw变化百分数比较均有显著差异(均P0.05)。结论超声造影定量参数PI及Pw变化百分数在抗血管治疗早期有明显差异,提示超声造影评估早期治疗疗效有一定应用价值。     

不可切除结直肠癌肝转移的转化性治疗策略

手术是治疗结直肠癌肝转移最有效的也是惟一有可能治愈的手段,但是大多数结直肠癌肝转移病人并不能够行肝转移灶切除手术。近些年,用各种细胞毒药物和（或）靶向药物等使不可切除的肝转移病灶缩小,转化为可切除,继而行手术切除,从而获得治愈的可能。转化性治疗的目的是获得最佳反应率,而不是获得最大反应率。术前转化性化疗应选择高效化疗方案,并尽量缩短疗程。具体方案选择方面,KRAS野生型病人推荐西妥昔单抗联合FOLFOX/FOLFIRI,其中5-氟尿嘧啶持续给药,而KRAS突变型病人考虑贝伐珠单抗联合两药化疗或者三药化疗方案。在行转化性治疗时,一旦转移灶转化为可切除,应积极手术切除。     

贝伐单抗联合IFL方案治疗转移性结直肠癌的临床研究

目的评价贝伐单抗联合IFL方案（伊立替康、氟尿嘧啶、亚叶酸钙）治疗既往接受过以草酸铂为主的化疗方案的进展期转移性结直肠癌的疗效和安全性。方法回顾性总结2004年7月至2006年6月间分别予以贝伐单抗联合IFL方案（A组,30例）和单纯使用IFL方案（B组,32例）进行化疗患者的治疗后反应率、治疗中不良反应和治疗前后血清肿瘤标志物的动态变化及随访1年的生存率。结果A组和B组的有效率分别为30．0％和21．8％;疾病控制率分别为80％和50％。所有患者治疗前后肿瘤标志物的浓度均有明显变化（P〈0．05）,A组与B组比较,差异有统计学意义（P〈0．05）。两组均未出现明显的Ⅲ、Ⅳ度不良反应,两组间不良反应的差异无统计学意义（P〉0．05）。A、B两组患者1年存活率分别为26．7％和18．8％,中位疾病进展时间分别为5．9个月和3．9个月,中位总生存期分别为10．9个月和8．9个月。差异均有统计学意义（P〈0．05）。结论与单纯使用IFL方案相比．贝伐单抗联合IFL方案能进一步延长既往接受过以草酸铂为主化疗方案的转移性结直肠癌患者的生存时间．治疗耐受性良好。     

分子靶向药物在胃肠道肿瘤综合治疗中的应用

分子靶向药物在晚期胃肠道肿瘤治疗中,被证实可提高患者的客观缓解率并延长总生存期.因此,其在局部进展期胃肠道肿瘤综合治疗中的价值被逐渐重视.曲妥珠单抗用于HER-2基因阳性的局部进展期胃癌新辅助化疗中的临床研究正在进行中,结果值得期待.大量研究证明,西妥昔单抗联合化疗对于KRAS基因野生型潜在可切除的结直肠癌肝转移患者,能提高手术切除率并延长总生存期;而贝伐珠单抗在KRAS基因突变型结直肠癌肝转移术前转化治疗中的作用正在评估中.对于可切除的结直肠癌肝转移,虽现有的证据显示,分子靶向药物在新辅助治疗中未能带来长期生存益处,但最终结论仍存议甚多.对于局部进展期直肠癌患者,新辅助化疗中的西妥昔单抗在二期临床研究中未能显示治疗获益,贝伐珠单抗的作用同样需要在三期临床研究后进一步证实.与晚期肿瘤单一治疗模式不同,在肿瘤综合治疗中,需要系统评估分子靶向药物与细胞毒药物、手术以及放疗之间可能的相互影响及协同作用,制定出科学并适用于临床实践的综合治疗模式.     

肝移植治疗不可切除性直肠癌肝转移1例

本例不可切除性直肠癌肝转移患者确诊直肠癌时已合并肝内不可切除多发转移, 切除原发病灶后采用FOLFOX方案化疗+贝伐珠单抗靶向治疗。2年后患者肝内转移灶增多增大, 未见肝外转移灶及原位复发, 实施肝移植手术, 术后采用他克莫司+西罗莫司免疫抑制方案, 雷替曲塞化疗。肝移植3年后, 本例患者肿瘤复发, 总生存期为6年。本例提示, 对于不可切除性结直肠癌肝转移患者, 在未发现原位复发及其他远隔转移的情况下实施肝移植手术可以提高患者的生活质量并获得较好的预后。     

669例结直肠癌同时陛和异时性肝转移患者不同治疗策略的预后分析

目的评价结直肠癌肝转移不同类型及治疗策略对肝转移患者生存的影响。方法回顾分析复旦大学附属中山医院2000年1月1日至2008年6月31日收治的669例结直肠癌肝转移患者的病例资料。结果本组患者同时性肝转移379例,异时性[发生肝转移中位时间（21．0±19．6）个月]肝转移290例。患者性别、年龄和肠道原发病灶的部位两组差异无统计学意义（P〉0．05）：而肝转移灶特征（累及肝叶类型、病灶个数和病灶直径）和术前CEA、CA19—9水平两组差异有统计学意义（P〈0．05）。手术切除肝转移灶253例．其中同时性肝转移123例,异时性肝转移130例。以2008年10月31日为随访终点,随访率100％。同时性肝转移和异时性肝转移的中位生存时间分别为11和23个月（P〈0．01）。5年生存率分别为6．4％和11．4％（P〈0．01）;手术病例与各种非手术治疗（介入、化疗、射频、无水酒精注射和中医中药）病例的中位生存期分别为37个月和5～26个月（P〈0．01）;5年生存率分别为35．6％和0～3．6％（P〈0．05）。结论手术治疗目前仍是结直肠癌肝转移的首选治疗措施：异时性肝转移患者生存率好于同时性肝转移。     

贝伐珠单抗联合FOLFOX方案治疗进展期结直肠癌的临床疗效和安全性Meta分析

目的系统评价贝伐珠单抗联合FOLFOX方案治疗进展期结直肠癌的临床疗效和安全性。方法以"Bevacizumab、FOLFOX、Advanced Colorectal Cancer、Randomized Controlled Trial"为英文检索词,以"贝伐珠单抗、FOLFOLX、进展期结直肠癌、随机对照试验"为中文检索词,计算机检索Pubmed、EMBSE、中国知网等中英文数据库从建库到2018年12月的相关文献,按照治疗方法分为联合组(贝伐珠单抗联合FOLFOX方案)和对照组(单独使用FOLFOX方案),使用Revman5.3软件进行Meta分析。结果本研究最终纳入11篇相关的随机对照研究,样本量为3178例,其中联合组1599例,对照组1579例。Meta分析结果显示,联合组客观缓解率(OR=3.15,95%CI:2.25~4.40,Z=6.71,P<0.00001)和疾病控制率(OR=2.73,95%CI:1.91~3.90,Z=5.49,P<0.0001)均高于对照组,在不良反应方面,联合组胃肠道反应发生率高于对照组(OR=1.29,95%CI:1.07~1.55,Z=2.64,P=0.008),肝损伤、白细胞减低、高血压、神经毒性等发生率两组间差异无统计学意义。结论贝伐珠单抗联合FOLFOX方案治疗进展期结直肠癌较单纯FOLFOX方案更加有效,但会增加胃肠道反应的发生风险。     

大肠癌肝转移术前化疗后的最佳手术时机

化疗联合手术治疗已逐渐成为结直肠癌肝转移病人的标准治疗方式。对于可切除的大肠癌肝转移病人是否需要术前化疗仍存在争议。存在预后不良因素时应接受术前化疗,术前化疗不应＞6周期。不可切除的肝转移病人均应接受术前化疗,术前化疗后定期复查,如转化为可切除,应立即切除。一般认为,停用化疗4周后可以手术切除肝转移灶,但如果联合贝伐单抗,应在停止治疗6~8周后进行手术。     

腹腔镜下结直肠癌根治术中联合腹腔热灌注化疗的临床研究

目的:探讨腹腔镜下结直肠癌根治术中联合腹腔热灌注化疗(IHPC)的安全性及可行性。方法:将120例进展期结直肠癌患者随机分成治疗组和对照组,每组各60例。两组患者均接受腹腔镜下结直肠癌根治术,治疗组术中行IHPC联合术后m FOLFOX6方案静脉化疗;对照组单纯行术后m FOLFOX6方案静脉化疗。比较两组患者手术相关指标、术后恢复情况、术后并发症、不良反应、局部复发率及远处转移率。结果:两组患者在手术相关指标、术后恢复情况、术后并发症方面差异均无统计学意义(均P>0.05);治疗组术后低蛋白血症和低钠血症的发生率明显高于对照组(20.0%vs.6.7%;15.0%vs.3.3%,均P<0.05);腹腔局部复发率和远处转移率明显低于对照组(6.7%vs.18.3%;8.3%vs.23.3%,均P<0.05);两组短期总生存率相当(P>0.05)。结论:腹腔镜下结直肠癌根治术中IHPC联合术后静脉化疗安全可靠,对局部复发及远处转移疗效较好。     

Conversion Therapy Using mFOLFOX6 With Panitumumab for Unresectable Liver Metastases From Multiple Colorectal Cancers With Familial Adenomatous Polyposis

A 39-year-old man received a diagnosis of unresectable multiple liver metastases from multiple colorectal cancers with familial adenomatous polyposis. After construction of an ileostomy, modified FOLFOX6 (mFOLFOX6) with panitumumab was administrated because rectal cancer and sigmoid colon cancer are KRAS wild type. The 13 courses of chemotherapy resulted in a marked reduction in the size of liver metastases and sigmoid colon cancer. Consequently, curative resection with total colectomy, ileal pouch anal anastomosis, and liver metastasis resection with radiofrequency ablation was performed. Progression of KRAS wild-type rectal cancer after chemotherapy suggested that each clone from rectal and sigmoid colon cancer might have a different sensitivity to epidermal growth factor receptor antibody. Immunohistochemical analysis revealed loss of PTEN expression in rectal cancer compared with liver metastases from sigmoid colon cancer, showing that the difference of mFOLFOX6 with panitumumab might be related to activation of the PI3K-AKT pathway.Key words: Panitumumab, mFOLFOX6, Colorectal cancer, Liver metastases, Familial adenomatous polyposisThe only available treatment associated with long-term survival in patients with liver metastases from colorectal cancer is complete liver tumor resection, with 5-year survival rates ranging from 25% to 57%.¹ However, only 40% to 50% of patients with colorectal metastasis to the liver are eligible for surgical resection.² Therefore, other liver metastasis patients undergo palliative chemotherapy to stabilize the disease and prolong their overall survival.During the past decade, the biggest advance made regarding unresectable liver metastases from colorectal cancer has been the ability of oncologists to convert inoperable liver disease to resectable disease using various molecular targeting drugs.^3,4 Several clinical studies have shown that the association of chemotherapy with bevacizumab (vascular endothelial growth factor monoclonal antibody), or cetuximab [epidermal growth factor receptor (EGFR) monoclonal antibody] is particularly promising in improving the resectability rate and, ultimately, survival.⁵Panitumumab is a fully human monoclonal antibody that binds specifically to the EGFR, and consequently, severe panitumumab-related infusion reactions are rare. Panitumumab, when added to FOLFOX4 (folinic acid, 5-fluorouracil, and oxaliplatin), increased response rate and improved progression-free survival in previously untreated metastatic colorectal cancer.⁶ Retrospective analyses of phase 3 trials of anti-EGFR antibodies, including cetuximab and panitumumab, found KRAS status to be an important predictive marker of efficacy, with only wild-type patients benefiting from treatment.⁷Here, we report a successful conversion therapy using modified FOLFOX6 (mFOLFOX6) plus panitumumab in a patient with familial adenomatous polyposis (FAP) who had unresectable multiple liver metastases from multiple colorectal cancers. To the best of our knowledge, we are the first researchers to demonstrate treatment of multiple target tumors derived from different clones with mFOLFOX6 and panitumumab, and to show differential panitumumab sensitivity for multiple primary tumors and liver metastases.     

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。     

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??The best timing of preoperative chemotherapy for liver metastases of colorectal cancer XING Bao-cai, WANG Hong-wei. Department of Hepato-bilio-pancreatic Surgery I, Peking University School of Oncology??Beijing Cancer Hospital??Beijing 100142, China
Corresponding author??XING Bao-cai, E-mail??xingbaocai88@sina.com
Abstract The combination of surgery and chemotherapy has become the standard treatment for patients with liver metastases of colorectal cancer. There is controversy that preoperative chemotherapy should be considered in patients with resectable liver metastases of colorectal cancer. The patients with prognostic factor of poor survival should be received preoperative chemotherapy. Surgery should be performed after a maximum of 6 cycles of preoperative chemotherapy. In patients with unresectable liver metastases, there is no question regarding the indication of chemotherapy. They should be carefully monitored and performed surgery as soon as the metastases become resectable. Surgery can be performed after 4 weeks from the last cycle of chemotherapy, and 6-8 weeks following chemotherapy plus bevacizumab.     

腔镜下微波消融联合术后经脐静脉插管化疗治疗结直肠癌肝转移

目的探讨腹腔镜结直肠癌切除及脐静脉插管同期微波消融联合术后化疗治疗肝转移的临床疗效。方法在腹腔镜下对1I例结直肠癌肝转移行结直肠癌切除及经肝圆韧带脐静脉插管置泵,同期行肝脏转移瘤微波消融治疗,术后辅以经化疗泵介入化疗。比较治疗前后肿瘤直径大小、血供及坏死情况。结果本组治疗前CT检测转移瘤直径为（4．2±2．5）cm,治疗后为（2．5±1．2）cm,转移瘤结节完全坏死8例（72．7％）。随访时间〉6个月者10例,生存10例;随访时间〉12个月者8例,生存6例。结论腹腔镜结直肠癌切除及脐静脉插管同期微波消融联合术后化疗治疗肝转移的疗效好,值得临床推广。     

结直肠癌伴不可切除的同时性肝转移的腹腔镜治疗

目的:探讨结直肠癌伴有同时性不可切除肝转移灶的腹腔镜治疗的可行性及临床应用价值。方法:回顾分析2011年6月至2012年12月31例结直肠癌伴不可切除的同时性肝转移患者的临床资料及随访结果。按原发灶手术切除方式分为两组,A组行开腹手术切除结直肠癌原发灶(n=18),B组行腹腔镜手术(n=13)。术后均采取mFOLFOX6方案化疗。对比分析两组患者手术时间、术中出血量、术后排气时间、术后住院时间、术后接受首次化疗时间及治疗效果。结果:31例均成功施行结直肠癌切除术,腹腔镜组无一例中转开腹及严重并发症发生。术后患者行mFOLFOX6方案化疗至少2个周期。经统计学分析发现,两组患者手术时间、治疗效果差异无统计学意义(P>0.05),但腹腔镜组术中出血量明显减少(P<0.01),术后排气时间明显缩短(P<0.05),术后住院时间明显减少(P<0.05),术后接受首次化疗的时间明显缩短(P<0.05)。结论:对于不可切除的同时性结直肠癌肝转移患者,行腹腔镜原发肿瘤切除是安全、可行的;与开腹手术相比,腹腔镜手术治疗结直肠癌伴不可切除的同时性肝转移,在切除原发灶的手术中具有出血量少、创伤小、术后肠功能恢复快、住院时间明显缩短并促进术后早期化疗等优势。腹腔镜手术对原发肿瘤及转移灶的治疗效果与开腹手术无明显差别,具有良好的临床应用价值。     

Echogenicity of liver metastases is an independent prognostic factor after potentially curative treatment

HYPOTHESIS: Intraoperative echogenic appearance of liver metastases from colorectal cancer is a prognostic factor of outcome after curative treatment. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Department of Surgery at a university hospital. PATIENTS: One hundred forty-three consecutive patients with hepatic metastases from colorectal cancer who underwent liver resection with curative intent between 1992 and 1998. INTERVENTION: Curative treatment was achieved by liver resection alone, liver resection plus edge cryotherapy, or liver resection plus cryotherapy to lesions not amenable to further resection. In patients with more than 2 lesions, a hepatic artery catheter was placed for regional chemotherapy. MAIN OUTCOME MEASURES: The echogenic appearance of the liver metastases was assessed by intraoperative ultrasound by a single person throughout the study using a 5-MHz ultrasound probe. The findings were prospectively entered into the database. RESULTS: Fifty-four percent of patients had hyperechoic metastases. This group had significantly longer overall (log rank, P<.001) and recurrence-free survival (log rank, P =.004) compared with patients who had hypoechoic metastases (36%). A significantly higher percentage of mucin-secreting tumors were found in the hypoechoic patient group (chi(2), P =.001). Dukes stage of the primary tumor (P =.02), echogenicity of the liver secondaries (P =.04), and diameter of the largest resected metastasis (P =.01) were independent prognostic factors for recurrence-free survival in the Cox regression model. CONCLUSION: These results support the hypothesis that echogenicity of liver metastases from colorectal cancer is an independent prognostic factor of outcome after curative resection.     

mFOLFOX6方案与奥沙利铂联合替吉奥治疗胃癌肝转移疗效对比

目的 比较mFOLFOX6方案与奥沙利铂联合替吉奥治疗胃癌肝转移患者的疗效及其对患者免疫功能的影响.方法 选择2014年1月-2016年1月收治的134例胃癌肝转移患者作为研究对象,采用随机数字表法分为观察组和对照组,每组67例.观察组患者给予奥沙利铂联合替吉奥进行治疗.对照组患者给予mFOLFOX6方案进行治疗(奥沙利铂+亚叶酸钙+5-氟尿嘧啶),各组均治疗4个疗程.治疗后观察各组患者临床疗效及不良反应发生情况;治疗前及治疗各疗程后评价两组患者卡氏评分;治疗前后分别抽取各组患者静脉血,检测其中CD3+、CD4+、CD8+及CD19+等免疫功能相关指标水平.采用SPSS 22.0软件分析相关数据,计量资料以((x)±s)表示,采用t检验;计数资料以百分数表示,采用x2检验.结果 治疗后,观察组总有效率为52.2％,明显高于对照组的38.8％(P＜0.05);治疗第3疗程及第4疗程后,观察组KPS评分分别为(81.3±9.7)分和(83.2±9.9)分,均明显高于对照组(P＜0.05);治疗后,观察组CD3+、CD4+、CD8+及CD19+含量分别为(54.21±6.38)％、(24.11±2.41)％、(21.33-±3.16)％及(7.18±1.13)％,均明显高于对照组(P＜0.05);观察组各项不良反应发病率均明显低于对照组(P＜0.05).结论 奥沙利铂联合替吉奥治疗胃癌肝转移患者的疗效优于mFOLFOX6方案,对免疫功能的影响小于mFOLFOX6方案,且安全性更佳.     

术中射频联合门静脉置化疗泵治疗结直肠癌肝转移的临床分析

目的观察术中射频联合门静脉置化疗泵治疗结直肠肝转移的疗效、生存期及安全性。方法治疗组10例患者术中切除结直肠原发肿瘤,并术中行肝转移瘤射频消融术及门静脉置化疗泵化疗,对照组既往20例除姑息切除原发肿瘤,术中未行其它治疗。结果治疗组总有效率明显优于对照组,治疗组有效率70.0%,而对照组有效率10.0%,差异有显著性意义(P<0.05);观察治疗组和对照组的1、3、6、12和18个月生存率,治疗组为100%,100%,80.0%,60.0%和60.0%,对照组为70.0%,50.0%,30.0%,5.0%和0,两组差异有显著性意义(P<0.05)。结论术中射频联合门静脉置化疗泵可有效治疗结直肠癌肝转移。