对比微波消融与肝切除术治疗结直肠癌肝转移效果:Meta分析

目的采用Meta分析对比微波消融(MWA)与肝切除术(LR)治疗结直肠癌肝转移(CRCLM)的效果和安全性。方法检索PubMed、Embase、Cochrane Library、中国生物医学文献数据库、万方、中国知网、维普数据库关于MWA与LR治疗CRCLM的文献,检索时间自建库至2020年8月31日。依据纳入及排除标准筛选文献,以Review Manager 5.3和Stata 14软件进行Meta分析。结果最终纳入13篇文献、共1 534例CRCLM患者,MWA组685例,LR组849例。经异质性检验,1年总体生存率(OS)(I~2=0%,P=0.72)、3年OS(I~2=0%,P=0.86)、5年OS(I~2=0%,P=0.90)均无明显异质性,采用固定效应模型进行分析,结果显示MWA组与LR组间1年OS[HR=0.99,95%CI(0.95,1.02),P=0.44]、3年OS[HR=1.02,95%CI(0.93,1.11),P=0.74]差异均无统计学意义,LR组5年OS高于MWA组[HR=0.82,95%CI(0.69,0.97),P=0.02]。异质性检验示并发症无明显异质性(I~2=0%,P=0.78),以固定效应模型进行分析,结果显示MWA组并发症发生率低于LR组[RR=0.35,95%CI(0.23,0.52),P0.000 01)]。结论 MWA治疗CRCLM早、中期疗效(1、3年OS)与LR相当,远期疗效(5年OS)不及LR,但安全性更高。     

结直肠癌肝转移瘤热消融治疗国际专家共识分享

肝转移是结直肠癌致死的最主要原因,手术切除是其首选治疗方式。然而,临床可手术切除的肝转移瘤仅占全部肝转移瘤的10%~25%,对不可切除的肝转移瘤通常采用系统化疗和/或局部消融治疗。近年来热消融技术的治疗效率和安全性日益提高,术后患者5年生存率高于单纯化疗。2013年国际消融专家组发布了结直肠癌肝转移瘤热消融治疗国际专家共识,基于射频消融相关应用的长期随访文献,总结热消融治疗在结直肠癌肝转移瘤治疗中的具体推荐及相关适应证。本文对该共识的主要内容进行介绍与分享。     

射频消融治疗结直肠癌肝转移的研究进展

结直肠癌肝转移(CRLM)是结直肠癌治疗中的难点问题,也是结直肠癌患者最主要的死亡原因。近年来,射频消融(RFA)作为肝肿瘤局部治疗的手段之一,被探索性地应用于CRLM的综合治疗中,显示出微创、安全、有效、可重复治疗等优势。本文将综述RFA及其联合其他治疗手段治疗不同分期CRLM的研究进展,期望为CRLM综合治疗提供更...     

经皮射频治疗结直肠癌肝转移31例

目的 评价B超引导经皮射频（PRFA）治疗结直肠癌肝转移的疗效。方法 应用PRFA治疗结直肠癌肝转移31例共55个病灶，肿瘤直径1．5～8．5cm。应用RF2000射频仪和10电极LeVeen针，病灶〉2．5cm者予分层多点叠合毁损，〉5．0cm或多发者配合肝动脉导管化疗栓塞术（TACE）及无水酒精注射疗法（PEI），随访观察病灶影像形态表现、血清CEA变化和患者生存率。结果 PRFA后反应期3～7d，包括局部疼痛不适、发热、ALT升高等；并发肝曲结肠穿孔和腹壁穿刺道转移各1例；小肿瘤（〈3．0cm）完全坏死率达92．9％（26／28），3．1～5．0cm的肿瘤完全坏死率为73．3％（11／15），病灶〉5cm者均未完全坏死；1、2、3年生存率分别为87．1％、77．5％和54．8％。结论 PRFA是治疗结直肠癌肝转移的一种微创疗法，对〈3．0cm肿瘤疗效显著，对大肿瘤可联合TACE、PEI等进行综合治疗。     

超声引导经皮微波消融治疗肝转移癌的临床疗效分析

目的分析超声引导经皮微波消融(MWA)治疗肝转移癌的疗效。方法应用超声引导下经皮MWA技术治疗肝转移癌共27例69个结节,直径为0.9～13.2(3.0±2.0)cm。观察局部疗效、局部复发率、再发率及生存率。所有病例均签署知情同意书。结果判断局部疗效的完全消融(CA)率为92.8%(64/69),其中,结节直径3.0cm、3.0～5.0cm及≥5.0cm组的CA率分别为100%(34/34)、92.3%(24/26)和66.7%(6/9),直径≥5.0cm组CA率明显低于其他两组(P0.05)。结节局部复发率为9.4%(6/64),其中结节直径3.0cm、3.0～5.0cm及≥5.0cm组的结节复发率分别为2.9%(1/34)、16.7%(4/24)和16.7%(1/6)。判断肝内其他部位出现新转移灶的再发率为44.4%(12/27)。随访时间为3～34(17.0±8.7)个月。6个月、1年及2年的累积生存率分别为88.9%、63.0%及34.4%,平均生存期17.8个月,中位生存期19.0个月。结论经皮MWA治疗肝转移癌的局部疗效满意,对复发或再发病例可以反复治疗,能够延长生存期。     

超声引导下射频消融治疗肝转移瘤的疗效观察

目的评价超声引导下射频消融（RFA）治疗结直肠癌肝转移瘤（MLC）的疗效。方法采用超声引导下RFA治疗结直肠癌MLC患者60例134个病灶,其中91个病灶≤3.0 cm,43个〉3.0 cm。术前39例血清癌胚抗原（CEA）增高,21例正常。采用CEUS检查结合增强CT、穿刺活检及CEA值的动态变化综合评价肿瘤治疗效果。结果术后3个月复查CEA,37例增高,23例正常。术后30 min CEUS检查显示127个射频消融病灶呈无灌注区,近期有效率达94.78%（127/134）。术后1个月CEUS检查显示8个病灶局部增强,考虑复发,经超声引导下穿刺活检及细胞学检查证实而行第2次治疗。术后1个月增强CT复查显示126个（126/134,94.03%）射频消融病灶呈无灌注区,为完全坏死的转移病灶;部分坏死病灶为8个,与CEUS结果一致。结论超声引导下RFA是治疗MLC的一种安全有效的局部微创治疗方法。     

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。     

结直肠癌切除同期射频消融联合化疗治疗肝转移

目的：探讨结直肠癌切除同期射频消融联合化疗治疗肝转移的临床疗效。方法：对39例病人先行原发肿瘤的切除，同期行射频消融联合化疗治疗肝转移，以螺旋CT增强扫描为主结合彩超综合评价治疗效果。结果：39例共82个肝转移病灶，完全坏死率85％。随访时间〉6个月者3l例，生存27例；随访时间〉12个月11例，生存8例。结论：结直肠癌切除同期射频消融联合化疗治疗肝转移的疗效较好，值得临床推广。     

腹腔镜下结直肠癌肝转移一期手术23例临床疗效

目的探讨腹腔镜下治疗结直肠癌肝转移一期的安全性及有效性。方法回顾分析2011年1月至2013年6月行结直肠癌肝转移手术的43例患者的临床资料,将23例患者同时行腹腔镜切除肝转移灶切除术纳入腹腔镜组,20例患者同时行开放性肝转移灶切除术患者纳入开腹组。采用SPSS 23.0软件进行分析,中位生存时间、生存率及术后并发症比较采用χ2检验;计量资料采用(x珋±s)表示,比较采用独立样本t检验,生存分析采用Kaplain-Meire法计算生存率。P0.05表示差异有统计学意义。结果腹腔镜组患者手术时间及术后腹腔引流管留置时间较开腹组显著减少(P0.05);两组患者术中出血量、术后肛门排气时间及术后住院时间差异无统计学意义(P0.05);两组患者术后生存率相近,无围手术期死亡病例,术后均未见严重术后并发症。结论腹腔镜下结直肠癌肝转移一期联合切除安全可行,具有较好的疗效。     

Occult hepatic metastases in colorectal carcinoma

Occult hepatic metastases (OHMs) were detected by ultrasound and/or CT scanning in 17 of 71 (24 per cent) patients undergoing apparently curative resection for colorectal carcinoma. One of the patients with OHMs survived 5 years; in contrast, only 5 of 54 patients without evidence of OHMs at surgery died of disseminated disease. The presence or absence of OHMs at the time of surgery predicts the majority of deaths from disseminated disease following apparently curative resection for colorectal carcinoma.     

Intraoperative hepatic lymphatic mapping in patients with liver metastases from colorectal carcinoma

The survival of patients undergoing liver resection for colorectal metastases is poor in the presence of extrahepatic disease. Therefore identification of periportal and celiac lymph node metastases is central to proper patient selection. In this study we examined the technique of intraoperative hepatic lymphatic mapping with isosulfan blue dye in humans. Intrahepatic dye injection was performed in patients undergoing surgical exploration for colorectal liver metastases. The location of all blue-stained lymphatics and lymph nodes was recorded. All stained and unstained lymph nodes were biopsied for pathologic examination. Thirteen intraoperative lymphatic mapping procedures were performed in 11 patients. A blue-stained lymphatic was visualized in 11 of 13 injections (85%). A blue lymph node was visualized in seven of 13 injections (54%). Three of the seven blue nodes (43%) were not detected by the surgeon before the mapping procedure. There were no complications associated with the intrahepatic dye injections. All biopsied lymph nodes were negative for metastatic tumor. We conclude that intraoperative hepatic lymphatic mapping with isosulfan blue dye is a simple, rapid, and safe technique in humans. It may serve as an adjunct to random lymph node biopsy for the identification of periportal and celiac nodal metastases before liver resection in patients with metastatic colorectal carcinoma.     

Growth rate of hepatic metastases in colorectal carcinoma

The rates of growth of 29 hepatic metastases from 15 patients with primary colorectal carcinoma were studied using serial computed tomography (CT). Eleven metastases were found by the surgeon at laparotomy (overt metastases); the remaining eighteen were not evident to the surgeon at laparotomy, but were detected by CT scan during the immediate postoperative period (occult metastases). An estimate of tumour volume doubling time was obtained from a semi-logarithmic plot of tumour cell number against time. The mean doubling time for the overt metastases was 155 +/- 34 days (+/- s.e.m.) compared with 86 +/- 12 days (P less than 0.05) for the occult metastases. The age of the metastases at the time of surgery was estimated by extrapolation of the observed growth curve assuming Gompertzian kinetics. The mean age of the overt metastases was 3.7 +/- 0.9 years (+/- s.e.m.) The corresponding age of the occult metastases was 2.3 +/- 0.4 years.     

The treatment of hepatic metastases in colorectal carcinoma

Colorectal carcinoma is the third most common cause of cancer death in the United States, with 135,000 new cases and 55,000 deaths annually. Ultimately, two-thirds (99,000) of all patients with colorectal cancer will develop metastasis to the liver and other organs in their life span, making metastatic colorectal cancer the second leading cause of cancer-related death in North America. The optimal management of these patients has become increasingly complex with the myriad of treatment options that are available. Because the timing of any therapy (surgery, chemotherapy, or others) has become integral to the success of the treatment, a collaborative approach involving multiple specialties is needed for the best patient outcome. Defined clinical and pathologic determinants of outcome have been demonstrated to effect the overall and disease-free survival of patients with metastatic colorectal cancer. Understanding of these determinants remains essential to any treating physician and has lead to significant paradigm shifts in the management of patients with metastatic colorectal cancer.     

Imaging strategies in hepatic metastases from colorectal carcinoma

Approximately two-thirds of metastatic lesions that develop following curative resection of colorectal cancer occur in the liver and lung. In select groups of patients, resection of these lesions is associated with increased 5-year survival. In the liver, precise preoperative documentation of the presence, location, number, and relationship of these lesions to vascular structure is crucial in the selection of candidates for curative resection. Computed tomography with arterial portography (CTAP), intraoperative ultrasonography (IOUS), positron emission tomographic (PET) scan, and radionuclide scanning, including radiolabeled monoclonal antibody imaging, are emerging as the procedures of choice in the preoperative and intraoperative evaluation of metastatic colorectal cancer to the liver.     

Effect of hepatic artery chemotherapy on survival of patients with hepatic metastases from colorectal carcinoma treated with cryotherapy

Thirty-eight patients with unresectable multiple liver metastases from colorectal carcinoma were treated with either hepatic artery chemotherapy (HAC) and cryotherapy (n=27) or cryotherapy alone (n=11). Follow-up survival data were summarized using Cox regression. Allowing for the effect of the pathology of the primary tumor and the preoperative carcinoembryonic antigen (CEA) level, those patients who did not receive HAC after cytoreduction were three times as likely to die as those given HAC (RR 3.3, 95%; CI 1.2–9.3). The estimated median survival of patients treated with cryotherapy alone was 245 days, whereas for those given more than 3 months of HAC plus cytoreduction therapy it was 570 days. It is recommended that all patients who receive cryotherapy for multiple liver metastases from colorectal rectal carcinoma be given subsequent hepatic artery chemotherapy.

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Resumen En el presente estudio, 38 pacientes con metástasis hepáticas múltiples y no resecables de carcinoma colo-rectal fueron tratados con quimioterapia administrada en la arteria hepática (HAC) y crioterapia (n=27) o crioterapia sola (n=11). Los datos del seguimiento fueron resumidos según el método de regresión de Cox. Teniendo en cuenta el efecto de la patología del tumor primario y el nivel preoperatorio de antígeno carcino-embrionario, se halló que aquellos pacientes que no recibieron HAC luego de la citorreducción tuvieron una probabilidad de muerte 3 veces mayor que los que recibieron HAC (RR 3.3, 95% CI 1.2 a 9.3). La sobrevida media estimada de los pacientes tratados con crioterapia sola fue de 245 días, en tanto que aquellos que recibieron HAC por tres meses y terapia de citorreducción fue de 570 días. Se recomienda que todos los pacientes que reciben crioterapia para metástasis hepáticas múltiples de carcinoma colo-rectal reciban luego quimioterapia por vía de la arteria hepática.

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Résumé Trente-huit patients ayant des métastases hépatiques multiples non reséquables d'origine colorectale ont été traités soit par chimiothérapie par voie artérielle (CVA) associée à la cryothérapie (n=27) soit par cryothérapie seule (n=11). Les survies ont été analysées selon la méthode d'analyse du Modèle de Cox. En tenant compte de l'effet de la pathologie de la tumeur primitive et du niveau préopératoire de l'ACE, les patients n'ayant pas eu de de décéder que ceux qui en ont eu (RR 3.3, 95% IC 12 à 9.3). L'estimation de la survie médiane des patients traités par la cytoréduction seule a été de 245 jours, alors que celle des patients traités par les deux avec une CVA d'au moins trois mois, a été de 570 jours. On recommande que tous les patients ayant des métastases multiples du foie à partir des cancers colorectaux aient une CVA par la suite.

     

Cell kinetics of hepatic metastases as a prognostic marker in patients with advanced colorectal carcinoma

Cell kinetics was determined, as 3H-thymidine labeling index (LI), in hepatic lesions from 36 patients with primary colorectal carcinoma: LI values ranged from 0.9% to 23.5% and were normally distributed. Cell kinetics was not related to sex or age of the patient, or to liver function. For clinical studies the median LI value of 10% was used to separate slowly and rapidly proliferating lesions. Univariate analysis showed that patients radically resected and with a low LI tumor have a longer disease-free interval and a better probability of 12-month survival than those non-radically resected and with a high LI tumor. When treatment and cell kinetics were taken into consideration, the probability of 12-month survival was 100% for patients with slowly proliferating and radically resected hepatic metastases. Patients with rapidly proliferating tumors, regardless of type of treatment, had the worst prognosis.     

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.