肝动脉化疗栓塞术治疗中晚期原发性肝癌的疗效观察

[目的]研究经导管肝动脉化疗栓塞术(TACE)治疗中晚期原发性肝癌的疗效并预测影响患者生存率的相关因素。[方法]80例中晚期原发性肝癌患者经1次或多次TACE治疗后,分别于治疗后第1、3、6、12个月对患者进行CT扫描评估肿瘤对治疗的反应并计算生存率。[结果]对所有患者随访观察3年(或者观察至死亡),80例患者共进行了163次TACE,按Child-pugh分级A级48例(60.0%),B级32例(40.0%);肿瘤大小5cm 18例(22.5%),5~10cm 42例(52.5%),10cm 20例(25.0%);行1、2、3、4次TACE的患者分别为12、56、9、3例;1、2、3年的总生存率分别为71.3%、43.8%和17.5%,肿瘤直径5cm患者TACE后3年生存率显著高于肿瘤直径为5~≥10cm患者。[结论]TACE是治疗中晚期肝癌的一种有效的方法,能有效缓解患者的临床症状并延长生存期,初始肿瘤的大小是决定患者生存率的独立影响因素。     

经肝动脉化疗栓塞术联合索拉非尼治疗原发性肝癌患者疗效与生存分析

目的 探讨经肝动脉化疗栓塞术（TACE）联合索拉非尼治疗原发性肝癌（PLC）患者的近期疗效和2 a生存情况。方法 2008年1月至2013年12月收治的PLC患者76例,排除远处转移患者。所有患者接受TACE治疗1～3次,44例同时接受索拉非尼治疗。按照2000年世界卫生组织制定的实体瘤治疗疗效评价标准（RECIST）考核疗效,应用Kaplan-Meier 法计算生存率。结果 在完成TACE治疗6月后,在44例接受索拉非尼治疗的患者中,死亡2例,在32例只接受TACE治疗的患者中,死亡3例。在生存的接受联合索拉非尼治疗的42例患者中,完全缓解、部分缓解、疾病稳定和疾病进展率分别为38.1%、50.0%、4.8%和7.1%,而在只接受TACE治疗的29例生存者中,则分别为27.6%、41.4%、13.8%和17.2%,两组差异显著（P<0.05）;联合组1 a和2 a生存率分别为68.2%和43.2%,而只接受TACE治疗组则分别为50.0%和31.3%,两组差异显著（P<0.05）。结论 对于未手术切除的肝癌患者,在进行TACE治疗的同时或以后给予索拉非尼维持治疗可以提高疗效,延长生存期。     

原发性肝癌治疗方法的评价——肝切除术前后肝动脉置管化疗栓塞治疗原发性肝癌

原发性肝癌手术前后辅助治疗中的一个重要手段就是经肝动脉置管栓塞化疗(TACE)。但对于能够手术切除的原发性肝癌，是否需要行TACE治疗和何时行TACE治疗仍存在着争论。其焦点在于，TACE治疗是否能提高手术切除率，减少术后复发，是否能改善患者的预后，选用什么样的TACE治疗方案才能充分发挥其治疗作用而使其副作用降到最低。     

经肝动脉化疗栓塞治疗原发性肝癌56例

2005年2月-2006年2月,我院采用经导管肝动脉化疗栓塞术（TACE）治疗原发性肝癌56例,取得满意疗效。现报告如下。     

肝动脉栓塞化疗术治疗原发性肝癌破裂出血的疗效

原发性肝癌是临床上最为常见的消化系统恶性肿瘤之一,由于其起病隐匿,没有特征性的临床表现,肿瘤的早期难以得到诊断,大多数患者在肿瘤的中晚期才获得确诊[1].晚期的原发性肝癌常常伴有身体其他地方的转移,其中肿瘤自发性破裂出血是原发性肝癌的并发症之一,常发生于老年原发性肝癌患者[2].肿瘤的自发性破裂出血给患者带来巨大痛苦的同时,可以因为急性失血而出现休克甚至死亡.本文观察肝动脉栓塞化疗术治疗原发性肝癌破裂出血的临床疗效.     

肝动脉栓塞化疗联合肝叶切除术治疗原发性肝癌患者临床疗效观察

目的 观察肝动脉栓塞化疗（TACE）联合肿瘤切除手术治疗原发性肝癌（PLC）患者的临床疗效。方法 2015年10月~2016年10月我院诊治的PLC患者95例,其中47例接受TACE治疗,48例在TACE治疗后1月行手术切除肿瘤治疗,观察并对比两组患者病灶根除和生存率情况。结果 联合组术后病灶清除率、术后1 a生存率、2 a生存率分别为100.0%、83.3%和68.8%,均显著高于TACE组的53.2%、61.7%和46.8%（P<0.05）,术后复发率为16.7%,明显低于对照组的51.1%（P<0.05）;治疗后联合组肝功能指标改善情况显著优于TACE组（P<0.05）;TACE组患者术后出现肺栓塞5例,肿瘤破裂出血2例,肺部感染3例,而联合组出现肺栓塞2例,肝断面胆瘘1例,肿瘤破裂出血1例,肺部感染1例（P<0.05）。结论 在TACE术后再行手术切除肿瘤治疗PLC患者具有一定的临床应用价值。     

经导管肝动脉化疗栓塞术治疗中晚期原发性肝癌患者的疗效与安全性再认识

目的 探讨经导管肝动脉化疗栓塞术治疗中晚期原发性肝癌患者的疗效以及安全性。方法 2015年7月~2016年8月在我院接受治疗的原发性肝癌患者45例,采用经导管肝动脉化疗栓塞术治疗。结果 在治疗后3 m行腹部CT检查,在45例PLC患者中,获得完全缓解15例（33.3%）,部分缓解16例（35.6%）,病情稳定6例（13.3%）,病情进展8例（17.8%）;随访3年,生存患者7例（15.6%）;术后不良反应可控,未影响治疗的进行。结论 采用经导管肝动脉化疗栓塞术治疗原发性肝癌患者,毒副反应发生率低,效果显著。     

介入栓塞和手术再切除治疗原发性肝癌术后复发患者的疗效

原发性肝癌(PLC)是常见的恶性肿瘤,简称为肝癌,其中包括肝细胞癌(HCC)、肝内胆管细胞癌等不同病理类型。手术治疗仍然是HCC的首选方法,但是术后患者复发率较高〔1,2〕。对于术后复发的PLC患者,如何有效延长患者生存时间是PLC外科治疗的目标。本文就我院收治的PLC术后复发患者采取介入栓塞和手术再切除治疗,对比疗效,旨在探讨治疗复发性肝癌的有效方法。     

双途径介入疗法治疗原发性肝癌疗效评价

目的　探讨双途径介入疗法 (下称双介入法 )治疗原发性肝癌的临床价值。方法　选择原发性肝癌患者 6 5例 ,对其中 34例单纯行肝动脉化疗栓塞 (TACE,对照组 ) ,31例行 TACE和分次多点经皮肝穿刺注射无水乙醇 (双介入法 ,观察组 )。全部病例定期做 CT检查和 AFP测定 ,观察肿瘤客观疗效。结果　对照组及观察组肿瘤客观有效率 (CR+PR)分别为 35 .3%、6 4 .4 % (P<0 .0 5 ) ;AFP下降幅度分别为 5 6 .1%、78.6 % (P<0 .0 5 ) ;2年存活率分别为 5 0 %、6 1.3% (P<0 .0 5 )。结论　双介入法治疗原发性肝癌疗效肯定 ,优于单纯应用 TACE。     

Associating liver partition and portal vein ligation for staged hepatectomy: the current role and development

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) has recently been developed to induce rapid liver hypertrophy and reduce posthepatectomy liver failure in patients with insufficient future liver remnant(FLR). ALPPS is still considered to be in an early developmental phase because surgical indications and techniques have not been standardized. This article aimed to review the current role and future developments of ALPPS.DATA SOURCES: Studies were identified by searching MEDLINE and Pub Med for articles from January 2007 to October 2016 using the keywords "associating liver partition and portal vein ligation for staged hepatectomy" and "ALPPS". Additional papers were identified by a manual search of references from key articles.RESULTS: ALPPS induces more hypertrophy of the FLR in less time than portal vein embolization or portal vein ligation.The benefits of ALPPS include rapid hypertrophy 47%-110% of the liver over a median of 6-16.4 days, and 95%-100% completion rate of the second stage of ALPPS. The main criticisms of ALPPS are centered on its high morbidity and mortality rates. Morbidity rates after ALPPS have been reported to be 15.3%-100%, with ≥ the Clavien-Dindo grade III morbidity of 13.6%-44%. Mortality rates have been reported to be 0%-29%.The important questions to ask even if oncologic long-term results are acceptable are: whether the gain in quality and quantity of life can be off balance by the substantial risks of morbidity and mortality, and whether stimulation of rapid liver hypertrophy also accelerates rapid tumor progression and spread. Up till now, the documentations of the ALPPS procedure come mainly from case series, and most of these series include heterogeneous groups of malignancies. The numbers are also too small to separately evaluate survival for different tumor etiologies.CONCLUSIONS: Currently, knowledge on ALPPS is limited, and prospective randomized studies are lacking. From the reported preliminary results, safety of the ALPPS procedure remains questionable. ALPPS should only be used in experienced, high-volume hepatobiliary centers.     

Arterial ischemia in the deportalized liver following associating liver partition and portal vein ligation for staged hepatectomy

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel 2-stage technique intended to induce rapid growth of the future liver remnant (FLR). Initial reports of a 12% mortality rate have sparked debate regarding the safety of the procedure. A 64 years old male was planned for a right-sided hemi-hepatectomy due to colorectal cancer liver metastases. Intra-operatively it was decided to convert to an ALPPS due to unexpectedly small segments 2-4. Post-operative serum laboratory tests indicated an acute liver failure and radiological imaging showed no sign of arterial blood flow to the right hemi-liver. A computed tomography examination on post-operative day 3 revealed that the FLR had increased from 290 to 690 mL in 3 d (138% growth). In the following days serum values gradually improved and stage 2 was carried out on post-operative day 7. The rest of the hospital stay was uneventful and the patient made a full recovery. ALPPS is a fascinating advancement in liver surgery. Despite severe post-operative complications, in properly selected cases it provides successful outcomes that other modalities of treatment cannot offer.     

Current status of associating liver partition with portal vein ligation for staged hepatectomy: Comparison with two-stage hepatectomy and strategies for better outcomes

Since its introduction in 2012, associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has significantly expanded the pool of candidates for liver resection. It offers patients with insufficient liver function a chance of a cure. ALPPS is most controversial when its high morbidity and mortality is concerned. Operative mortality is usually a result of post-hepatectomy liver failure and can be minimized with careful patient selection. Elderly patients have limited reserve for tolerating the demanding operation. Patients with colorectal liver metastasis have normal liver and are ideal candidates. ALPPS for cholangiocarcinoma is technically challenging and associated with fair outcomes. Patients with hepatocellular carcinoma have chronic liver disease and limited parenchymal hypertrophy. However, in selected patients with limited hepatic fibrosis satisfactory outcomes have been produced. During the inter-stage period, serum bilirubin and creatinine level and presence of surgical complication predict mortality after stage II. Kinetic growth rate and hepatobiliary scintigraphy also guide the decision whether to postpone or omit stage II surgery. The outcomes of ALPPS have been improved by a combination of technical modifications. In patients with challenging anatomy, partial ALPPS potentially reduces morbidity, but remnant hypertrophy may compare unfavorably to a complete split. When compared to conventional two-stage hepatectomy with portal vein embolization or portal vein ligation, ALPPS offers a higher resection rate for colorectal liver metastasis without increased morbidity or mortality. While ALPPS has obvious theoretical oncological advantages over two-stage hepatectomy, the long-term outcomes are yet to be determined.     

Role of associating liver partition and portal vein ligation for staged hepatectomy in colorectal liver metastases: A review

Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant (FLR) to allow for resection directly. There are therefore strategies to decrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion (PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.     

Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy

AIM To highlight the potential mechanisms of regeneration in the Associating Liver Partition and Portal vein ligation for Stage hepatectomy models(clinical and experimental) that could unlock the myth behind the extraordinary capability of the liver for regeneration,which would help in designing new therapeutic options for the regenerative drive in difficult setup,such as chronic liver diseases. Associating Liver Partition and Portal vein ligation for Stage hepatectomy has been recently advocated to induce rapid future liver remnant hypertrophy that significantly shortens the time for the second stage hepatectomy. The introduction of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in the surgical armamentarium of therapeutic tools for liver surgeons represented a real breakthrough in the history of liver surgery. METHODS A comprehensive literature review of Associating Liver Partition and Portal vein ligation for Stage hepatectomy and its utility in liver regeneration is performed. RESULTS Liver regeneration after Associating Liver Partition and Portal vein ligation for Stage hepatectomy is a combination of portal flow changes and parenchymal transection that generate a systematic response inducing hepatocyte proliferation and remodeling. CONCLUSION Associating Liver Partition and Portal vein ligation for Stage hepatectomy represents a real breakthrough in the history of liver surgery because it offers rapid liver regeneration potential that facilitate resection of liver tumors that were previously though unresectable. The jury is still out though in terms of safety,efficacy and oncological outcomes. As far as Associating Liver Partition and Portal vein ligation for Stage hepatectomy-induced liver regeneration is concerned,further research on the field should focus on the role of nonparenchymal cells in liver regeneration as well as on the effect of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in liver regeneration in the setup of parenchymal liver disease.     

Maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model

AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, partial hepatecotmy(PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity.RESULTS Compared with PHx and sham groups, the proliferation of f LR was significantly higher in ALPPS group(P = 0.023 and 0.001 at second day, P = 0.034 and P 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPSinduced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration.CONCLUSION Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage Ⅱ of ALPPS should be performed prudently in patients with marginally adequate f LR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration.     

Outcomes of staged hepatectomies for liver malignancy

Liver malignancies are the fifth most common cause of death worldwide. Surgical intervention with curative intent is the treatment of choice for liver tumors as it provides long-term survival. However, only 20% of patients with metastatic liver lesions can be managed by curative liver resection. In most of the cases,hepatectomy is not feasible because of insufficient future liver remnant(FLR).Two-stage hepatectomy is advocated to achieve liver resection in a patient who is considered to not be a candidate for resection. Procedures of staged hepatectomy include conventional two-stage hepatectomy, portal vein embolization, and associating liver partition and portal vein ligation for a staged hepatectomy.Technical success is high for each of these procedures but variable between them.All the procedures have been reported as being effective in achieving a satisfactory FLR and completing the second-stage resection. Moreover, the overall survival and disease-free survival rates have improved significantly for patients who were otherwise considered nonresectable; yet, an increase in the morbidity and mortality rates has been observed. We suggest that this type of procedure should be carried out in high-flow centers and through a multidisciplinary approach. An experienced surgeon is key to the success of those interventions.     

肝动脉和门静脉栓塞化疗联合射频消融治疗原发性肝癌

目的探讨肝动脉栓塞化疗、门静脉栓塞化疗及射频消融治疗不能手术切除的原发性肝癌的临床价值。方法对不能手术切除的56例肝癌患者行肝动脉栓塞化疗联合经皮门静脉栓塞化疗及射频消融综合治疗,并于同期单纯行TACE治疗的病人60例作对照。结果两组病人的肝功能变化差异无显著性意义（均P〉0.05）;两组病人治疗后ATP转阴率差异有显著性意义（P〈0.05）;CR和PR有显著性差异（P〈0.01）;1年及2年生存率差异有显著性意义（P〈0.05）。结论对不能手术切除的肝癌患者行肝动脉栓塞化疗联合经皮门静脉栓塞化疗及射频消融综合治疗能显著提高AFP转阴率、总有效率及生存率,在临床上有较好的应用价值。     

Significance of morphological alteration by portal vein branch ligation in endotoxin-induced liver injury after partial hepatectomy.

BACKGROUND: Regenerating liver after partial hepatectomy (PH) is susceptible to endotoxin. This study was conducted to investigate how morphological alteration by preoperative portal vein branch ligation (PVL) affects endotoxin-induced liver injury after PH. METHODS: Male Sprague-Dawley rats were divided into a PVL group undergoing left PVL and into a non-PVL group receiving a sham operation. Seven days later, animals in both groups were subjected to PH (the left lateral, median and caudate lobes). Lipopolysaccharide (LPS) was intravenously administered to both groups 2 days after PH. RESULTS: A significant increase in hepatocyte and sinusoidal endothelial cell proliferation assessed by Ki-67 immunostaining reached a peak at day 2 and 3 after PVL, respectively, in accordance with the changes in plasma interleukin-6 concentrations after PVL. The proliferation response of these cells after PH was observed in both groups, showing a significantly weaker response in the PVL group. The sinusoidal width after PH was significantly reduced in the non-PVL group when compared with that in the PVL group. LPS administration induced a marked elevation of plasma tumour necrosis factor-alpha levels in the non-PVL group compared with the PVL group. PVL before PH significantly attenuated endotoxin-induced functional and structural liver damage with greater hepatic polymorphonuclear leucocyte infiltration and microcirculatory derangement, resulting in an improvement in the 7-day survival rate. CONCLUSIONS: Morphological alteration by PVL is of great advantage in preventing the development of endotoxin-induced liver injury in the regeneration process after PH.     

Simultaneous transcatheter arterial chemoembolization and portal vein embolization for patients with large hepatocellular carcinoma before major hepatectomy

BACKGROUND Sequential transarterial chemoembolization(TACE) and portal vein embolization(PVE) are associated with long time interval that can allow tumor growth and nullify treatments' benefits.AIM To evaluate the effect of simultaneous TACE and PVE for patients with large hepatocellular carcinoma(HCC) prior to elective major hepatectomy.METHODS Fifty-one patients with large HCC who underwent PVE combined with or without TACE prior to hepatectomy were included in this study,with 13 patients in the simultaneous TACE + PVE group,17 patients in the sequential TACE + PVE group,and 21 patients in the PVE-only group.The outcomes of the procedures were compared and analyzed.RESULTS All patients underwent embolization.The mean interval from embolization to surgery,the kinetic growth rate of the future liver remnant(FLR),the degree of tumor size reduction,and complete tumor necrosis were significantly better in the simultaneous TACE + PVE group than in the other groups.Although the patients in the simultaneous TACE + PVE group had a higher transaminase levels after PVE and TACE,they recovered to comparable levels with the other two groups before surgery.The intraoperative course and the complication and mortality rates were similar among the three groups.The overall survival and disease-free survival were higher in the simultaneous TACE + PVE group than in the other two groups.CONCLUSION Simultaneous TACE and PVE is a safe and effective approach to increase FLR volume for patients with large HCC before major hepatectomy.