ALPPS与门静脉栓塞治疗未来剩余肝脏体积不足肝癌临床疗效的Meta分析

目的:探讨联合肝脏分隔和门静脉结扎的分阶段肝切除术（associating liver partition and portal vein ligation for staged hepatectomy,ALPPS）和门静脉栓塞（portal vein embolization,PVE）两种术式治疗未来剩余肝脏（future liver remnant,FLR）体积不足肝癌的可行性、安全性和有效性。方法:通过检索PubMed、Web of Science、Embase、Cochrane、中国知网、万方、维普数据库中有关ALPPS与PVE治疗FLR不足肝癌临床疗效对比的所有文献,检索时间为数据库建库至2021年05月。采用RevMan 5.3软件对数据进行分析。结果:共纳入17篇文献,含1 145例患者。进行荟萃分析后显示:在二步手术完成率（OR=9.62,95%CI:5.35～17.28）、R0切除率（OR=2.01,95%CI:1.05～3.83）方面ALPPS组与PVE组之间的差异具有统计学意义（P<0.05）,ALPPS组可显著改善患者的二步手术完成率及R0切除率;在90天病死率、术后肝功能衰竭率、总体并发症发生率、3年生存率方面ALPPS组与PVE组之间的差异无统计学意义（P均>0.05）。结论:ALPPS相较PVE在治疗FLR不足肝癌时可显著改善患者的二步手术完成率及R0切除率,且两者有相似的围手术期疗效及肿瘤学结局。     

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.     

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.     

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.     

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.     

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.     

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。     

Assessment of future remnant liver regeneration after portal vein embolization using three‐dimensional CT and MR volumetric analyses

The purpose of this study is to portray right portal vein embolization (PVE) as a valuable technique that helps in expanding the volume of the left liver lobe and discuss the relevant published work. We describe our experience with four patients who underwent PVE and analyse the value of CT and MRI in the preoperative evaluation of these patients. Four patients with hepatic malignancy (hepatocellular carcinoma) (n = 2) and metastatic liver disease (n = 2) underwent portal vein occlusion. PVE was carried out in three patients using polyvinyl alcohol and stainless steel coils. Portal vein ligation was carried out in the fourth patient. In patients who were candidates for right hepatectomy, CT volumetric analysis was carried out before the surgery to assess the total liver volume and the future remnant liver, which is the residual left hepatic volume (in cases of right hepatectomy) or left lateral segment volume (in cases of right tri‐segmentectomy). Because the left lobe volumes were insufficient, patients were selected to undergo right PVE. Computed tomography volumetry was carried out 2–4 weeks after embolization to assess left hepatic lobe regeneration. Magnetic resonance volumetric analysis was carried out in two patients before and after embolization. All four patients had significant regeneration of the left lobe and tolerated the surgery with uneventful postoperative recovery.     

A nomogram to predict early postoperative recurrence of hepatocellular carcinoma with portal vein tumour thrombus after R0 liver resection: A large-scale,multicenter study

BackgroundPortal vein tumour thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch or above of the main portal vein (MPV) could benefit from R0 liver resection (LR). A nomogram is needed to predict early postoperative recurrence (ER) in HCC patients with PVTT and to guide selection of these patients for adjuvant therapy to reduce postoperative recurrence risks.MethodsHCC patients with PVTT limited to a first-order branch or above of the MPV after R0 LR as an initial therapy were included. A nomogram using data from a retrospective training cohort was developed with the Cox regression model. The model was tested in a prospective internal validation cohort and three external validation cohorts.ResultsOf 979 patients, 657 developed postoperative ER (67.1%). ER occurred in 165 of 264 patients (62.5%) in the training cohort, 146 of 218 patients (70.0%) in the internal validation cohort, and 204 of 284 patients (71.8%), 77 of 113 patients (68.1%), and 65 of 100 patients (65%) in the three external validation cohorts, respectively. The nomogram included the following variables: hepatitis B surface antigen (HBsAg), PVTT, HBV DNA, satellite nodules, α-fetoprotein, and tumour diameter. The ROC were 0.836, 0.763, 0.802, 0.837, and 0.846 in predicting ER in the five respective cohorts.ConclusionA nomogram was developed and validated to predict postoperative ER in patients with HCC with PVTT after R0 LR. This nomogram could select appropriate patients with high ER risks for postoperative adjuvant therapy.     

Impact of neoadjuvant chemotherapy on post-hepatectomy regeneration for patients with colorectal cancer liver metastasis – Systematic review and meta-analysis

BackgroundToday, there is still debate on the impact of neoadjuvant chemotherapy (NeoChem) on liver regeneration (LivReg). The objectives of this study were to assess the impact of NeoChem and its characteristics (addition of bevacizumab, number of cycles and time from end of NeoChem) on post-hepatectomy LivReg.Material & methodsStudies reporting LivReg in patients submitted to liver resection were included. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases were searched. Only studies comparing NeoChem vs no chemotherapy or comparing chemotherapy characteristics from 1990 to present were included. Two researchers individually screened the identified records registered in a predesigned database. Primary outcome was future liver remnant regeneration rate (FLR3). Bias of the studies was evaluated with the ROBINS-I tool, and quality of evidence with the GRADE system. Data was presented as mean difference or standard mean difference.ResultsEight studies with a total of 681 patients were selected. Seven were retrospective and one prospective comparative cohort studies. In patients submitted to major hepatectomy, NeoChem did not have an impact on LivReg (MD 3.12, 95% CI -2,12–8.36, p 0,24). Adding bevacizumab to standard NeoChem was associated with better FLR3 (SMD 0.45, 95% CI 0.19–0.71, p 0.0006).DiscussionThe main drawback of this review is the retrospective nature of the available studies. NeoChem does not have a negative impact on postoperative LivReg in patients submitted to liver resection. Regimens with bevacizumab seem to be associated with better postoperative LivReg rates when compared to standard NeoChem.