Liver venous deprivation versus associating liver partition and portal vein ligation for staged hepatectomy for colo-rectal liver metastases: a comparison of early and late kinetic growth rates,and perioperative and oncological outcomes

BackgroundDifferent techniques have been developed to optimize the Future Liver Remnant (FLR). Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) have shown the higher hypertrophy rates, but their place in clinical practice is still debated.MethodsThirty-two consecutive ALPPS and LVD procedures for CRLM performed between December 2015 and December 2019 were included. This retrospective study evaluated kinetic growth rates (KGR) as primary outcome, and perioperative and oncological outcomes as secondary endpoints.ResultsA total of 17 patients underwent LVD before surgery, whereas 15 underwent ALPPS. On early evaluation (7 vs 9 days, respectively), KGR did not differ between ALPPS and LVD cohort (0.8% per day vs 0.3% per day, p = 0.70; 23 cc/day vs 26 cc/day, p = 0.31). Late evaluation (21 vs 9 days) showed a KGR significantly decreased in the LVD group (0.6% per day vs 0.2% per day, p = 0.21; 20 cc/day vs 10 cc/day p = 0.02). Mean FLR-V increase was comparable in the two groups (60% vs 49%, p 0.32). Successful resection rate was 100% and 94% in LVD and ALPPS group, respectively. The hospital stay (p < 0.0001) and severe complications rate (p = 0.05) were lower after LVD. One and 3-years overall survival (OS) were 72,7% and 27,4% in the ALPSS group, versus 81,3% and 54,7% in LVD group (p = 0.10). The Median DFS was comparable between both techniques (6.1 months and 5.9 respectively, p = 0.66).ConclusionsLVD and ALPPS shows similar KGR during the early period following preparation as well as similar survival outcomes. Hospital stay and severe complications are lower after LVD.     

腹腔镜辅助联合肝脏离断和门静脉结扎的二步肝切除术治疗原发性肝癌的安全性和疗效评价

目的探讨腹腔镜辅助联合肝脏离断和门静脉结扎的二步肝切除术（associating liver partition and portal vein ligation for staged hepatectomy , ALPPS ）治疗原发性肝癌的安全性和疗效。方法回顾性分析2013年12月本院收治的一例巨块型肝癌患者以腹腔镜辅助ALPPS方法切除肿瘤的临床资料。第1步在腹腔镜下结扎门静脉右支并离断左肝内外叶;第2步在第1次术后第8天,评估剩余肝脏体积能满足机体要求后行右半肝的扩大切除术,同时对患者围术期的临床指标和随访资料进行分析。结果第1次手术出血50 ml,手术时长225分钟。第2次手术出血700 ml,手术时长335分钟。切除右肝三叶大小约24．0 cm×22．0 cm×15．0 cm,重量2．7 kg,肿瘤大小约18．0 cm×16．0 cm×14．0 cm,残余肝大小约15．0 cm×13．0 cm×8．0 cm。术后病理结果为原发性肝细胞癌。术后患者出现胆漏,经保守治疗后治愈。术后随访2个月,残余肝再生体积达约1200 ml,AFP降至150 ng／ml,未发现肿瘤复发转移。术后随访至32个月,再次评估残余肝再生体积达约1300 ml,AFP 16 ng／ml,未发现肿瘤复发转移,无疾病生存期达32个月。结论腹腔镜辅助ALPPS手术可作为残肝体积不足的一些较晚期肝癌患者的治疗选择。     

Dealing with insufficient liver remnant: Associating liver partition and portal vein ligation for staged hepatectomy

Liver resection for colorectal liver metastases has emerged to highly successful treatment in the last decades. Key to this success is complete hepatic tumor removal and systemic disease control by chemotherapy. Associating liver partition and portal vein ligation for staged hepatectomy is the most recent two-stage resection strategy for patients with very small future liver remnant making complete tumor removal possible within 1 to 2 weeks. Oncological outcome data are being collected at the moment and first results from small series reveal promising results.     

门静脉癌栓形成与肝癌干细胞转移的关系

近期的干细胞研究提示门静脉癌栓(PVTT)可能与肝癌干细胞在门静脉微环境诱导下的定向转移有关,肝癌干细胞脱离原发病灶,外渗到细胞外基质,促进血管的生成或细胞内渗,从而进入循环系统,逃避宿主的防御机制,通过趋化作用迁移到特定的门静脉内皮黏附,归巢到特定的微环境,形成门静脉癌栓.     

联合肝脏分隔和门静脉结扎的二步肝切除术的应用现状和疗效评价

联合肝脏分隔和门静脉结扎的二步肝切除术(associating liver partition and portal vein ligation for staged hepatectomy,ALPPS)即两期手术根治肝脏肿瘤,一期手术对患侧肝门静脉分支的结扎及左右肝脏实质的离断,使预留肝脏体积在短期内快速增生,以保证二期手术切除病肝后足以代偿肝脏功能.虽然研究表明ALPPS能够提高部分肝癌患者的总体生存,为残余肝体积不足的肝脏肿瘤患者提供一种新的手术方式,但ALPPS自诞生后就争议不断,并迅速成为研究热点.本文结合笔者自身临床经验和最新循证医学证据,对ALPPS手术应用现状及临床价值进行述评.     

Technical modifications and outcomes after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) for primary liver malignancies: A systematic review

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) represents a novel surgical technique which provides rapid and effective liver regeneration allowing for the resection of lesions initially deemed unresectable. The objective of this systematic review is to summarize all technical modifications of the original ALPPS approach (mALPPS) for primary liver malignancies and evaluate short- and long-term outcomes. A systematic search of the literature was conducted using PubMed, Scopus, Cochrane Library Central, Google Scholar, and clinicaltrials.gov databases until July, 31 2019. The following keywords were utilized: “Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy”, “ALPPS”, “Portal Vein Embolization (PVE) And In Situ Split”, “Portal Vein Ligation (PVL) And In Situ Split”. A total of 24 studies were identified incorporating data on 83 patients who underwent a mALPPS for a primary liver malignancy. Median FLR hypertrophy after ALPPS-1 was 54% (range, 6.7–133%) and median EBL during the ALPPS 1 and ALPPS 2 stages was 200 mL (range 0–1000) and 700 ml (range 100–4000), respectively. R0 resections were achieved in all patients (100%). Most complications occurred post ALPPS- 2 (n = 33/72, 45.8%), while overall 30-day mortality was 13.3%. After a median follow up of 7 months (range 3–60), recurrence rate was 18.9%. Disease-free survival ranged from 3 to 60 months with a median of 10 months and overall survival ranged from 3 to 60 months with a median of 11 months. ALPPS with the various technical modifications offers a reasonable chance of complete tumor resection among patients with initially unresectable primary liver tumors. Further advances in patient selection, surgical techniques and perioperative management are required to minimize complications rates. Large scale prospective trials are needed to validate the role of the technical modifications of ALPPS in the treatment of patients with primary liver malignancies in an individualized setting.     

Two stage hepatectomy (TSH) versus ALPPS for initially unresectable colorectal liver metastases: A systematic review and meta-analysis

BackgroundAlthough numerous comparisons between conventional Two Stage Hepatectomy (TSH) and Associating Liver Partition and Portal Vein Ligation for staged hepatectomy (ALPPS) have been reported, the heterogeneity of malignancies previously compared represents an important source of selection bias. This systematic review and meta-analysis aimed to compare perioperative and oncological outcomes between TSH and ALPPS to treat patients with initially unresectable colorectal liver metastases (CRLM).MethodsMain electronic databases were searched using medical subject headings for CRLM surgically treated with TSH or ALPPS. Patients treated for primary or secondary liver malignancies other than CRLM were excluded.ResultsA total of 335 patients from 5 studies were included. Postoperative major complications were higher in the ALPPS group (relative risk [RR] 1.46, 95% confidence interval [CI] 1.04–2.06, I² = 0%), while no differences were observed in terms of perioperative mortality (RR 1.53, 95% CI 0.64–3.62, I² = 0%). ALPPS was associated with higher completion of hepatectomy rates (RR 1.32, 95% CI 1.09–1.61, I² = 85%), as well as R0 resection rates (RR 1.61, 95% CI 1.13–2.30, I² = 40%). Nevertheless, no significant differences were achieved between groups in terms of overall survival (OS) (RR 0.93, 95% CI 0.68–1.27, I² = 52%) and disease-free survival (DFS) (RR 1.08, 95% CI 0.47–2.49, I² = 54%), respectively.ConclusionALPPS and TSH to treat CRLM seem to have comparable operative risks in terms of mortality rates. No definitive conclusions regarding OS and DFS can be drawn from the results.     

Comparative study of right portal vein ligation versus embolisation for induction of hypertrophy in two-stage hepatectomy for multiple bilateral colorectal liver metastases

Aim

In patients with two-stage hepatectomy (TSH) for multiple bilobar liver metastases from colorectal cancer, few clinical series compare functional remnant hypertrophy of the liver volume between right portal vein ligation (PVL) and embolisation (PVE). Our objective is to analyse the effectiveness of portal vein ligation to achieve hypertrophy of the functional remnant volume (FRV) of the liver and to compare the results with portal vein embolisation in a series of patients with multiple bilobar liver metastases from colorectal carcinoma.

Patients and methods

Between September 2001 and September 2011 we performed a TSH in 41 patients with multiple bilobar colorectal liver metastases. A right PVL was performed in 23 patients with an insufficient FRV (three patients did not complete the second stage due to tumour progression and were excluded). We prospectively compare these results with the increased remnant volume obtained in 18 patients with right PVE.

Results

The median FRV was higher in the patients with PVE, rising from 501 ml (range 309–703) to 636 ml (range 387–649), than those with PVL, rising from 510 ml (range 203–824) to 595 ml (range 313–1213) (p < 0.05). The median %FRVI was higher in the patients with PVE (median 40%; range 21–65%) than those with PVL (median 30%; range 21–60%) (p < 0.05).

Conclusions

PVL and PVE were effective in all cases for obtaining hypertrophy of the FRV before major liver resection. Right PVE obtains better results and should be used where necessary to achieve a further increase in volume.     

Prediction of portal vein invasion by hepatocellular carcinoma: a correlations between portal vein tumor thrombus and biochemical tests.

Hepatocellular carcinoma patients were categorized into three grades according to the extent of portal vein invasion by the tumor. Correlations between the extent of portal vein invasion and values of alpha-fetoprotein (AFP), and various biochemical tests were examined. The extent of portal vein invasion by the tumor significantly correlated with the values of glutamic oxaloacetic transaminase (GOT), glutamic oxaloacetic transaminase: glutamic pyrubic transaminase (GOT:GPT), lactic dehydrogenase (LDH), alkaline phosphatase, leucinaminopeptidase (LAP), gamma-glutamic transpeptidase (gamma-GTP) and log10AFP. Results of the multivariate logistic regression analysis showed the values of LAP, LDH, log10AFP and GOT:GPT to be statistically significant independent indicators of portal vein invasion by hepatocellular carcinoma. The calculated probability for portal vein tumor thrombus, which was derived from the results of a step wise multivariate logistic regression procedure, revealed high accuracy and specificity for predictability. To design effective therapy and to predict the prognosis, it would be beneficial to obtain additional information from this calculated probability in patients with hepatocellular carcinoma.     

原发性肝癌合并门静脉癌栓的放射治疗进展

原发性肝癌合并门静脉癌栓的发病率相当高,治疗效果差、生存期短、合并症多,一直是肝癌研究领域中重要且难度高的课题。近年来放射治疗运用于原发性肝癌合并门静脉癌栓的报道越来越多,包括三维适形放疗、立体定向放疗、质子放疗、同位素内放疗以放疗为主的综合治疗等,主要根据患者的病情及癌栓情况合理制定治疗措施,进行个体化和序贯性的治疗。本文就放射治疗原发性肝癌合并门静脉癌栓的相关研究进展作一综述。     

基于列线图构建和验证肝细胞癌伴门静脉癌栓患者肝切除术后的预后评估模型

目的 分析影响肝细胞癌伴门静脉癌栓（PVTT-HCC）患者肝切除术后预后的影响因素,并基于列线图模型构建和验证预后评估模型。方法 本研究为回顾性队列研究,选择2008年1月—2017年11月在本院行肝切除术的PVTT-HCC患者为研究对象,随访截至2021年1月。主要预测结局为1、3、5年总生存率。按照7∶3的比例将患者随机分为训练集和验证集,在训练集中采用Cox比例风险回归分析影响预后的影响,并基于影响因素构建列线图模型。同时在训练集和验证集中采用C-index评价模型的区分度,一致性曲线评估模型的校准度。结果 共231例患者符合纳入排除标准纳入分析,其中训练集162例,验证集69例。Cox比例风险回归模型显示,AFP≥400 μg/L、AST≥40 U/L、ALP≥80 U/L、肿瘤个数>1个及肿瘤包膜不完整是影响预后的危险因素。在训练集中,列线图模型预测1、3、5年总生存率的C-index分别为0.826（95%CI: 0.791~0.861）、0.818（95%CI：0.782~0.854）、0.781（95%CI：0.742~0.820）,在验证集中分别为0.814（95%CI：0.777~0.851）、0.798（95%CI：0.758~0.837）、0.769（95%CI：0.728~0.810）。校正曲线显示列线图模型在训练集和验证集均有较好的校准度。结论 本研究构建的列线图模型可准确预测PVTT-HCC患者的预后。     

重视门静脉癌栓在原发性肝癌中的发生和演变

 原发性肝癌属中国高发常见的恶性肿瘤,门静脉癌栓是晚期肝癌的生物学标志之一,治疗棘手,预后极差。文章系统地介绍了门静脉癌栓的形成机制、诊断方法、分型和转归,为合理认识和积极治疗这一临床难题提供基础。     

肝癌合并门静脉癌栓的研究

门静脉癌栓(PVTT)是影响肝癌患者预后的重要因素.PVTT的形成是一个多因素、多环节的过程.根据门静脉的解剖特征及癌栓的生长规律,将PVTT分为Ⅰ～Ⅳ型.手术治疗、介入治疗、放疗为主的综合治疗模式提高了疗效.     

Portal vein embolization effect on colorectal cancer liver metastasis progression: Lessons learned

Colorectal liver metastasis (CRLM) is the major cause of death in patients diagnosed with colorectal cancer. The gold standard treatment of CRLM is surgical resection. Yet, in the past, more than half of these patients were deemed unresectable due to the inadequate future liver remnant (FLR). The introduction of efficient portal vein embolization (PVE) preoperatively allowed more resections of metastasis in CRLM patients by stimulating adequate liver hypertrophy. However, several experimental and clinical studies reported tumor progression after PVE which critically influences the subsequent management of these patients. The underlying pathophysiological mechanism of tumor progression post-PVE is still not fully understood. In spite of the adverse effects of PVE, it remains a potentially curative procedure in patients who would remain otherwise unresectable because of the insufficient FLR. Currently, the challenge is to halt tumor proliferation following PVE in patients who require this technique. This could potentially be achieved by either attempting to suppress the underlying oncologic stimulus or by inhibiting tumor growth once observed after PVE, without jeopardizing liver regeneration. More research is still required to better identify patients at risk of experiencing tumor growth post-PVE.     

术前选择性门静脉栓塞在大肠癌肝转移患者中的应用

大肠癌多发性肝转移灶切除后剩余肝脏组织太少,易导致术后肝功能不全或肝功能衰竭,限制了手术的应用。术前门静脉栓塞术(PVE)通过使栓塞侧肝叶萎缩,诱使对侧肝叶代偿性增生肥大,使原来不能耐受肝切除的患者能够安全地接受手术治疗。现综述术前选择性门静脉栓塞术在大肠癌肝转移应用中的病理生理学基础、临床适应证及疗效。     

超声引导下经皮肝穿刺门静脉插管治疗肝癌

目的:探讨B超引导下经皮肝穿刺门静脉插管的可行性、操作技术及其在肝癌介入治疗中的应用价值。方法:在超声引导下,选用微创穿刺器械,对31例肝癌患者进行经皮肝穿刺门静脉插管及药盒系统植入。结果:31例(100%)患者经皮肝穿刺门静脉插管获得成功,未出现严重并发症。结论:采用超声引导经皮肝穿刺门静脉插管是一种可供选择的门静脉插管方法。     

激光消融治疗肝癌门静脉癌栓93例报告

目的探讨经皮、经肝门静脉穿刺激光消融治疗肝癌门静脉癌栓的疗效及其临床意义。方法对肝癌门静脉癌栓患者行经皮经肝门静脉穿刺激光消融治疗,观察患者术后的生存率、癌栓的变化、癌栓支门静脉血流的变化及临床症状、肝功能和腹水等的变化情况。结果93例门静脉癌栓患者行激光消融治疗后6个月、1年和2年的生存率分别为82.8%、53.0%和34.1%。其中11例癌栓部分阻塞者的癌栓截面积在6个月时明显缩小;82例术前癌栓支门静脉完全无血流信号的患者,行激光治疗后第1天均观察剑彩色血流信号。1个月后67例、3个月后57例、6个月后40例、1年后27例、2年后4例患者癌栓部位门静脉支再次观察到彩色血流信号。38例激光消融(LA)治疗后生存1年的患者中,14例癌栓萎缩,直至消失;14例癌栓萎缩,门静脉呈蜂窝状改变;10例癌栓不缩小甚至继续生长,门静脉增宽。接受治疗后,患者临床症状、肝功能和腹水均得到不同程度的改善。结论激光消融治疗肝细胞癌门静脉癌栓,是一种疗效可靠、技术安全的新方法。     

腔内植入125I粒子条及支架联合经动脉化疗栓塞治疗原发性肝癌合并门脉主干癌栓的疗效

目的 探讨腔内植入125I粒子条及支架联合经动脉化疗栓塞(TACE)治疗原发性肝癌合并门脉主干癌栓的疗效.方法 采用腔内植入125I粒子条及支架联合TACE治疗50例肝癌合并门脉主干癌栓患者,并进行随访.结果 腔内共植入支架53枚,每例患者平均植入125I粒子15.8枚.技术成功率为100%,无严重的并发症.50例患者共接受137次TACE治疗,平均每例患者2.7次.肝内病灶客观缓解率为34.4%.50例患者平均生存期为370.1 d,中位生存期为223.0 d,术后90、180、360 d累积生存率分别为97.5%、59.3%和38.4%.支架平均通畅期为524.2 d,中位通畅期为407.4 d,术后90、180、360 d支架累积通畅率分别为94.9%、75.2%和64.5%.结论 腔内植入125I粒子条及支架联合TACE是治疗肝癌合并门脉主干癌栓的有效手段.

Abstract：

Objective To evaluate the therapeutic effect of endovascular placement of iodine-125 seed strand and stent combined with transcatheter arterial chemoembolization (TACE) to treat hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein (MPVTT). Methods Fifty patients with HCC complicated by MPVTT were enrolled into this study. There were 46 men and 4 women with a mean age of 53.9 years. TACE was performed after the iodine-125 seed strand and self-expandable stent placement in the obstructed segment of the main portal vein (MPV). Results Technical success rate was 100% for placement of iodine-125 seed strand and stent in the target segment of MPV. No serious procedure-related complications occurred. The mean follow-up duration was 208. 5 d. The mean and median survival time was 370.1 d and 223.0 d, respectively. The 90-, 180-, 360-day cumulative survival rates were 97.5%, 59.3%, and 38.4%, respectively. The mean and median patent time of stent was 524.2 d and 407.4 d, respectively. The 90-, 180-, 360-day cumulative patency rates of stent were 94.9%, 75.2%, and 64.5%, respectively. Conclusion Endovascular placement of iodine-125 seed strand and stent combined with TACE is an effective therapy for HCC with tumor thrombus in the main portal vein.