Portal Vein Ligation Research Articles

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in colorectal liver metastases: review of the literature

The liver is considered as one of the most common sites of metastasis and a key determining factor of survival in patients with isolated colorectal liver metastasis (CRLM). For longer survival of patients, surgical resection is the only available option. Especially in CRLM bilobar patients, to achieve R0 resection, maintaining an adequate volume of the future liver remnant (FLR) is the main technical challenge to avoid post-hepatectomy liver failure (PHLF). As standard procedures in the treatment of patients with severe metastatic liver disease, techniques such as portal vein embolization/portal vein ligation (PVE/PVL) accompanied by two-stage hepatectomy (TSH) have been introduced. These methods, however, have drawbacks depending on the severity of the disease and the capacity of the patient to expand the liver remnant. Eventually, implementation of the novel ALPPS technique ignited excitement among the community of hepatobiliary surgeons because ALPPS challenged the idea of unrespectability and extended the limit of liver surgery and it was reported that FLR hypertrophy of up to 80% was induced in a shorter time than PVL or PVE. Nonetheless, ALPPS techniques caused serious concerns due to the associated high morbidity and mortality levels of up to 40% and 15% respectively, and PHLF and bile leak are critical morbidity- and mortality-related factors. Carefully establishing the associated risk factors of ALPPS has opened up a new dimension in the field of ALPPS technique for improved surgical outcome by carefully choosing patients. The benefit of ALPPS technique is enhanced when performed for young patients with very borderline remnant volume. Adopting ALPPS technical modifications such as middle hepatic vein preservation, surgical management of the hepatoduodenal ligament, the anterior approach and partial ALPPS may lead to the improvement of ALPPS surgical performance. Research findings to validate the translatability of ALPPS’ theoretical advantages into real survival benefits are scarce.

Influence on the Kinetic Growth Rate after PVE and ALPPS

Purpose: "Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy" (ALPPS) and "Portal Vein Embolization" (PVE) have an important role in the treatment of malignant liver tumors. Both procedures induce rapid and effective hypertrophy of the future liver remnant (FLR) to prevent postoperative liver failure. The aim of this study is to determine impact factors on the kinetic growth rate (KGR) and subsequently FLR, in terms of complications, posthepatectomy liver failure (PHLF) and survival. Method: Patients undergoing ALPPS and PVE from 2010 until 2020 were included. KGR was defined as the quotient of hypertrophy and the time interval in weeks between intervention (PVE/ALPPS step 1) and resection. Results: Overall, 90 patients underwent ALPPS and 82 patients received PVE. The association between KGR and PHLF indicates a significant nonlinear effect in PVE (p=0.009) and ALPPS (p=0.05). For ALPPS, the incidence of PHLF significantly decreased from 30% to 8% (p=0,032) at cutoff value of KGR of >7 %/week. Patients with a KGR of >7%/week had a higher preoperative skeletal muscle index (p=0,029), but the same body mass index (p=0,301). Tumor anemia showed an association with a reduction of KGR (p=0,159). However, the KGR had no effect on postoperative morbidity, mortality, and long-term survival. For patients undergoing PVE, no valuable cutoff value for KGR could be calculated for a reduction of PHLF. Furthermore, the KGR was not influenced by preoperative metabolic or laboratory values. Conclusion: A KGR >7%/week showed a reduction of PHLF after ALPPS, but did not influence the morbidity and mortality. Skeletal muscle index and tumor anemia could be adjustable preoperative parameters to improve the KGR for patients undergoing ALPPS. For PVE, the KGR seems to be stable and no influencing factors could be found.

Modified Procedures for ALPPS Based on a Risk-Reduced Strategy: Paralleled Clinical Evaluation at Multiple Institutions.

PurposeWe compared the clinical outcomes of modified procedures for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) based on a risk-reduced strategy with those of classic ALPPS procedures in treating large liver carcinoma.Materials and MethodsShort-term outcomes, increases in future liver remnant (FLR) and functional FLR (FFLR), and overall survival (OS) were compared between 45 consecutive patients treated with modified ALPPS procedures and 34 patients treated with classic ALPPS procedures.ResultsClinical outcomes after the 1st-stage operation markedly improved with the modified procedures. Although the proportions of liver cirrhosis and hepatocellular carcinoma were higher in the modified group, the mortality and incidence of severe complications did not increase. FLR and FFLR hypertrophy at 1 week after the 1st-stage operation were similar in both groups; however, kinetic growth rates in the modified group were lower. OS rates were similar.ConclusionModified ALPPS procedures could be safely applied to provide long-term survival for patients with liver cirrhosis without sufficient FLR.

First Analysis of d-ALPPS, a Safe Alternative to ALPPS

Purpose: The “ideal” length of the inter-stage interval of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has not yet been investigated but many centres suggest that progression to the second stage within two weeks is crucial to achieve resection rates >95%, a key feature of ALPPS. However, without accurate volumetric and functional assessment of the future liver remnant (FLR), completion hepatectomy after one week might be too early, contributing to high morbidity and mortality.

ALPPS Procedure. The New Frontier in Advanced Liver Surgery. Single Centre Experience and Literature Review

Introduction: Presentation of the first experience of a liver surgery center in applying an innovative procedure - ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) for massive liver tumors. This medod has been performed in the surgery clinic 2 since 2018 in patients with massive primary or metastatic liver tumors, whose future residual liver volume is considered too small to perform curative liver resection safely. Until recently, these conditions assigned large tumors occupying more than 75-90% of the liver to the group of unresectable tumors. Prospectively, the ALPPS procedure was evaluated to convert unresectable liver tumors due to the small residual liver volume into resectable ones. Literature data were systematically reviewed using PubMed, Scopus, Google Scholar. Materials and methods: Since June 2018, 18 ALPPS procedures were performed in patients aged 62 +-8 years. Indications for surgical resection were liver metastases of colorectal cancer in 7 cases, perihilar cholangiocarcinoma in 4 cases, hepatocellular carcinoma in 6 cases, and GIST metastases 1 case. From the literature data we analyzed articles from 2014 to 2019. Results: Residual liver volume was calculated on CT angiography using the program included in the Siemens machine software and was 252 +- 115 ml (19.4 +- 6.2%) before ALPPS-1 and 542 +- 165 ml (30.7 +- 6.5%) before ALLPS-2 (P 0.001). The increase in residual liver volume between the two procedures was 60.4 +- 38% (range: 31-110%, P 0.001). The mean time between the first and second procedure was 9.4 +- 2.3 days. Average hospital stay was 28.4 +- 9.2 days. Postoperative morbidity 34.8%, mortality 0. Survival at 18 months was 100%. Conclusion: The ALPPS technique allows us to increase the resectability rate in patients with initially unresectable liver tumors with favorable postoperative outcomes. Careful selection of patients for a major complex procedure such as ALPPS allowed us to avoid postoperative mortality. Liver cirrhosis, cholestasis, and intraoperative hemorrhage are major factors for the development of postoperative morbidity.

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (Alpps) for Large Hepatocellular Carcinomas

Background: ALPPS was developed to induce accelerated future liver remnant (FLR) hypertrophy in order to increase hepatic tumour resectability and reduce the risk of post hepatectomy liver failure(PHLF).The only means of achieving long-term survival in hepatocellular carcinoma is complete tumor resection or liver transplantation. Patients with large hepatocellular carcinomas are currently not considered for liver transplantation.So, ALLPS is indicated in selected patients to induce rapid hepatic hypertrophy. Methods: Three patients initially presented with tumor measuring around 20-15 cm × 10-15cm in the right lobe of the liver. The liver was cirrhotic but liver function was normal in all 3 cases. CTvolumetry done and future liver remnant volume(FLRV) is < 40%. So we did ALLPS procedure to induce rapid and maximum hypertrophy in FLRV. During the first part of the procedure the right portal vein was ligated with complete liver parenchymal transection 1cm right of falciform ligament. The second procedure performed after 10-14 days with the division of right hepatic artery, right bile duct, right hepatic vein and liver segments 4-8 with tumor were removed. Results: >80% hypertrophy in FLRV was achieved in 10-14 days.Tumour was resected without developing PHLF . After 1 year follow up, patients are doing well with no signs of liver failure and recurrence Conclusion: ALPPS leads to sufficient hepatic hypertrophy within 2 weeks, avoiding PHLF in most patients. ALPPS should be considered in selected patients with large hepatocellular carcinomas.

Inhibition of TGFβ1 accelerates regeneration of fibrotic rat liver elicited by a novel two-staged hepatectomy.

Aims: Emerging evidence is demonstrating that rapid regeneration of remnant liver elicited by associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) may be attenuated in fibrotic livers. However, the molecular mechanisms responsible for this process are largely unknown. It is widely acknowledged that the TGFβ1 signaling axis plays a major role in liver fibrosis. Therefore, the aims of this study were to elucidate the underlying mechanism of liver regeneration during ALPPS with or without fibrosis, specifically focusing on TGFβ1 signaling.Approach: ALPPS was performed in rat models with N-diethylnitrosamine-induced liver fibrosis and no fibrosis. Functional liver remnant regeneration and expression of TGFβ1 were analyzed during the ALPPS procedures. Adeno-associated virus-shTGFβ1 and the small molecule inhibitor LY2157299 (galunisertib) were used separately or in combination to inhibit TGFβ1 signaling in fibrotic rats.Results: Liver regeneration following ALPPS was lower in fibrotic rats than non-fibrotic rats. TGFβ1 was a key mediator of postoperative regeneration in fibrotic liver. Interestingly, AAV-shTGFβ1 accelerated the regeneration of fibrotic functional liver remnant and improved fibrosis, while LY2157299 only enhanced liver regeneration. Moreover, combination treatment elicited a stronger effect.Conclusions: Inhibition of TGFβ1 accelerated regeneration of fibrotic liver, ameliorated liver fibrosis, and improved liver function following ALPPS. Therefore, TGFβ1 is a promising therapeutic target in ALPPS to improve fibrotic liver reserve function and prognosis.

Associating liver partition and portal vein ligation for staged hepatectomy for metastatic neuroendocrine tumor

Associating liver partition and portal vein ligation for staged hepatectomy for metastatic neuroendocrine tumor

Robotic ALPPS for intrahepatic cholangiocarcinoma

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for intrahepatic cholangiocarcinoma (ICC) demonstrated good long-term outcomes and can increase the rate of resectability in locally advanced ICC; however, the rates of postoperative complications (Clavien-Dindo grade III) and mortality range between 13.6 and 44% and 0 and 29%, respectively. Minimally invasive strategies may reduce the risk of postoperative morbidity, with the same oncologic outcomes. We herein report a full robotic ALPPS for advanced ICC. Methods: The patient was a 61-year-old male diagnosed with a 6.5 cm ICC involving segments IV, V, and VIII. The total clean liver volume was 1553 cc, with a future liver remnant (FLR) volume of 21.6% (segments I, II, and III: 337 cc). Results: Computed tomography scan on postoperative day (POD) 9 after stage 1 showed that FLR increased up to 38%. The indocyanine green clearance test showed a plasma disappearance rate of 19.8%/min and a retention rate at 15 min of 5.1%. ALPPS was completed on POD 14, the postoperative course was uneventful, and the patient was discharged in good general condition on POD 5. Final pathology showed a 6 cm ICC, G3, R0 margin (10 mm), T2-N0-M0. The patient started adjuvant capecitabine, and after 16 months he is in good general condition without signs of local or systemic recurrence. Conclusion: Robotic ALPPS combines the opportunity to perform a curative resection in patients presenting with insufficient FLR with the advantages of a minimally invasive approach. It is feasible and oncologically accurate for ICC when performed in fully trained HPB centers.

Health Economic Evaluation of Patients with Colorectal Liver Metastases Randomized to ALPPS or TSH - Analysis from the LIGRO Trial

Introduction: Two-staged hepatectomy (TSH), is an established method in advanced colorectal liver metastases (CRLM). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has emerged providing improved resection rate and survival. The health care costs and health outcomes, combining health related quality of life (HRQoL) and survival into quality-adjusted life years (QALYs), of ALPPS and TSH have not previously been evaluated and compared. Methods: This is a pre-planned, health economic evaluation from the LIGRO trial. One hundred patients with CRLM and standardized FLR < 30 % were randomized to ALPPS or TSH. Costs and QALYs were compared from treatment start up to 2 years. Costs are estimated from resource use, including all surgical interventions, length of stay after interventions, diagnostic procedures and chemotherapy and applying Swedish unit costs. QALYs were estimated by combining survival and HRQoL data, the latter being assessed with EQ-5D 3L. Estimated costs and QALYs for each treatment strategy were combined into an incremental cost-effectiveness ratio (ICER). Non-parametric bootstrapping was used to assess the joint distribution of incremental costs and QALYs. Results: The mean cost difference between ALPPS and TSH was 12662€, (95% CI -10728-36051, p=0.283). Corresponding mean difference in life years and QALYs was 0.1296 (95% CI -0.12-0.38, p=0.314) and 0.1285 (95% CI -0.11-0.36, p=0.28), respectively. The ICER was 93186 and 92414 for QALYs and life-years as outcomes, respectively. Conclusion: Based on the two-year data, the cost-effectiveness of ALPPS is uncertain. Further research, exploring cost and health outcomes beyond 2 year is needed.

Oncological benefits of portal vein embolization for patients with hepatocellular carcinoma.

Portal vein embolization (PVE) for hepatocellular carcinoma (HCC) was first introduced in 1986 and has been continuously developed throughout the years. Basically, PVE has been applied to expand the indication of liver resection for HCC patients of insufficient future liver remnant. Importantly, PVE can result in tumor progression in both embolized and non‐embolized livers; however, long‐term survival after liver resection following PVE is at least not inferior compared with liver resection alone despite the smaller future liver remnant volume. Five‐year disease‐free survival and 5‐year overall survival were 17% to 49% and 12% to 53% in non‐PVE patients, and 21% to 78% and 44% to 72% in PVE patients, respectively. At present, it has proven that PVE has multiple oncological advantages for both surgical and nonsurgical treatments. PVE can also enhance the anticancer effects of transarterial chemoembolization and can avoid intraportal tumor cell dissemination. Additional interventional transarterial chemoembolization and hepatic vein embolization as well as surgical two‐stage hepatectomy and associated liver partition and portal vein ligation for staged hepatectomy can enhance the oncological benefit of PVE monotherapy. Taken together, PVE is an important treatment which we recommend for listing in the guidelines for HCC treatment strategies.

The role of associating liver partition and portal vein ligation for staged hepatectomy in the management of patients with colorectal liver metastasis.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach emerged as a promising surgical strategy for rapid and large hypertrophy of the future liver remnant (FLR) when a major liver resection is necessary. Colorectal liver metastasis (CRLM) is their main indication. However, the promising results published so far, are very difficult to interpret since they usually focus on the technique and not on the underlying disease. Moreover, they are usually made up of complex populations, which received different chemotherapy schemes, with the ALPPS technical variations implemented over time and without consistent long-term follow-up results as well. Whereby, its role in CRLM should be analyzed as carefully as possible to indicate and select the best candidates who will benefit the most from this approach. We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to the ALPPS and CRLM.

Hepatectomía central combinada con ligadura de la vena porta derecha en un niño con hepatoblastoma bilobar: reporte de un caso

El hepatoblastoma es un tumor maligno, la resección quirúrgica es la meta del tratamiento. Paciente de 7 meses de edad con masa hepática en los segmentos IV A y B, V y VIII, clasificada como PRETEXT III, serealizó hepatectomía central conservando segmentos VI, VII, II , III y doble derivación biliodigestiva. La vena porta derecha involucrada, se ligó para producir hiperplasia compensadora izquierda, conservando el derecho como auxiliar. Hígado izquierdo en 14 días aumentó 48.1 %. Como alternativa al trasplante, en un tiempo quirúrgico se combinó hepatectomía central con ligadura de la vena porta derecha.

The role of associating liver partition and portal vein ligation for staged hepatectomy in unresectable hepatitis B virus-related hepatocellular carcinoma.

BackgroundThe role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for hepatocellular carcinoma (HCC) remains controversial.MethodsThe records of 23 consecutive patients with hepatitis B virus (HBV)-related HCC who underwent ALPPS at our center between November 2013 and June 2018 were retrospectively reviewed. Oncological results were compared between patients who received ALPPS and those that received transarterial chemoembolization (TACE) using propensity score matching (PSM) analysis.ResultsIn patients with a single tumor (n=12) the median tumor diameter was 13.0 (range: 5.1–20.0) cm, whereas in patients with multiple tumors (n=11) the median total tumor diameter was 6.3 (range: 2.3–26.0) cm. After the stage-1 ALPPS, the median future liver remnant (FLR) increased by 50.0%. The stage-2 ALPPS was completed in 20 patients (87.0%) after a median of 12 days. The 90-day mortality rate was 13% (3/23). The overall survival (OS) rates at 1-, 2-, and 5-year were 61.1%, 34.9%, and 8.7%, respectively, whereas the disease-free survival (DFS) rates at 1-, 2-, and 5-year were 27.8%, 27.8%, and 0.0%, respectively. PSM analysis showed no difference in OS between patients who underwent ALPPS and those that received TACE [P=0.178, Barcelona Clinic Liver Cancer (BCLC) stage A–C patients; P=0.241, BCLC stage B and C patients].ConclusionsALPPS is a safe and effective treatment option for unresectable HBV-related HCC. However, for HBV-related intermediate and advanced HCC patients, ALPPS may not be superior to TACE.

Synchronous Hemihepatectomy With Pancreatectomy Through Application of Associated Liver Partition and Portal Vein Ligation for a Metastatic Gastrinoma.

Synchronous Hemihepatectomy With Pancreatectomy Through Application of Associated Liver Partition and Portal Vein Ligation for a Metastatic Gastrinoma.

Colorectal liver metastases: Current management and future perspectives.

The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.

Efficacy and Safety of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Versus Two-Stage Hepatectomy: a Systematic Review and Meta-analysis

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been widely used in recent years. However, the clinical outcomes of ALPPS compared with that of two-stage hepatectomy (TSH) remain controversial. This meta-analysis aimed to compare the safety and efficacy of ALPPS and TSH. Relevant studies were retrieved via a search of the “MEDLINE,” “EMBASE,” and “SCIENCE DIRECT” databases. A meta-analysis of the mortality rate, second surgery completion rate, and future remnant liver regeneration rate was performed using the fixed-effects and random-effects models. A total of five studies were assessed that included 332 patients in the TSH group and 103 in the ALPPS group. The overall mortality rate in the ALPPS group (61.4%) was significantly higher as compared with that in the TSH group (39.1%) (χ2 = 11.23; Z = 4.77; P < 0.0001). The second surgery completion rate in the ALPPS group (92.2%) was significantly higher as compared with that in the TSH group (75.9%) (χ2 = 2.33; Z = 3.53; P = 0.0004). The average future remnant liver regeneration rate in the ALPPS group (69.5%) was significantly greater as compared with that in the TSH group (48.3%) (χ2 = 51.05; Z = 10.56; P < 0.0001). ALPPS can promote future liver regeneration, while TSH is associated with a lower mortality rate. The safety of ALPPS needs to be improved in further studies.

Safety, feasibility, and efficacy of associating liver partition and portal vein ligation for staged hepatectomy in treating hepatocellular carcinoma: a systematic review.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows radical resection of colorectal liver metastasis (CRLM). However, the effect of ALPPS on hepatocellular carcinoma (HCC) is not completely understood. This systematic review aimed to examine the existing data on the safety, feasibility, and oncologic effect of ALPPS on HCC. Electronic databases, including PubMed, Web of Science, and Embase, were systemically searched to identify articles on ALPPS and HCC. Additional articles were identified manually. The feasibility (liver hypertrophy between two stages), safety (90-day mortality), and therapeutic effect (long-term survival) were analyzed. Nine published articles that satisfied the retrieval standards were included, and these studies involved 176 patients. The evidence level of the enrolled studies was low, among which, the greatest Oxford evidence level was 2c. Additionally, the average median increase in future liver volume was 178 mL, the average interval between two stages was 11.2 days, the interval was remarkably longer in radiofrequency-assisted ALPPS (RALPPS) patients (28 days), and the average 90-day mortality was 17.6% (range, 0–50%). However, the oncological outcomes were not well documented. Survival following ALPPS was evidently improved compared with that after transcatheter arterial chemoembolization (TACE). This value was comparable to that following the one-stage hepatectomy and portal vein embolization (PVE), and it was similar to that in CRLM patients over the long term. Publication biases caused by case series and single-center reports are common in the review. It is concluded in this review that ALPPS is a safe and feasible approach to treat selected patients with unresectable HCC, but its oncological outcome requires further study. RALPPS is not recommended for HCC patients because of the long waiting time between the two stages.

The origin of newborn hepatocytes in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)-derived regeneration.

The origin of newborn hepatocytes in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)-derived regeneration.

Faster Return to Intended Oncologic Treatment (RIOT) After Trisectionectomy Does Not Translate to Better Outcomes.

Resection with trisectionectomy may necessitate liver molding for adequate future liver remnant (FLR), and subsequent complications can impact return to intended oncologic therapy (RIOT). This study evaluated whether a difference in RIOT exists with the use of molding and between liver molding techniques (associating liver partition and portal vein ligation for staged hepatectomy [ALPPS] and portal vein embolization [PVE]) with trisectionectomy. A retrospective review evaluated trisectionectomies for malignancy. Outcomes were compared with and without molding, and RIOT was determined. Fifty-one patients underwent trisectionectomy: 11 ALPPS, 14 PVE, 26 without molding. 73% of ALPPS, 64% of PVE, and 58% without molding achieved RIOT (P = .971). There were no differences found in baseline characteristics, R0 rate, length of stay, readmission, complications, or mortality. Time to RIOT was significantly different (ALPPS: 3.3 months; PVE: 5.2 months; none: 2.4 months, P = .0203). There were no differences in recurrence or survival. Liver molding should not cause apprehension as there are no differences in achieving RIOT. Although technique alters time to RIOT, this does not translate into improved outcomes, implicating disease biology, and regeneration stimulus.