Clinical Outcome and Future Liver Remnant Regenerative Response in Laparoscopic Versus Open ALPPS

NCT04868149 | Recruiting Phase 3

• 1 other identifier: UW20-599
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a new surgical procedure that induces rapid liver regeneration in patients with small liver remnant planning for major liver resection. It is a two-staged operation with stage I including portal vein ligation and splitting the right liver away from the left liver. After stage I, the left liver will undergo rapid liver regeneration and the stage II operation can be performed at 7-10 days after stage I operation when the liver remnant reaches an adequate size. In stage II operation, the right liver that contains the tumor is then removed. This surgical procedure was incepted in Germany in 2013 and was later started in Queen Mary Hospital in Hong Kong for the first time in December 2015. The initial indication was mainly for colorectal liver metastasis but due to the relatively high incidence of hepatocellular carcinoma in Hong Kong, HBP surgery team of Queen Mary Hospital has transferred this procedure to be applied for hepatitis-related hepatocellular carcinoma and so far, the centre has cumulated one of the largest single-center experience in the literature. Nonetheless, the usual approach for ALPPS involved open surgery and induced substantial surgical stress to the patient, especially after stage I operation. With the advent of minimally invasive liver surgery in recent years, the team has successfully applied laparoscopic surgery to ALPPS in 2019. Despite the advancement in laparoscopic surgical skills that rendered laparoscopic ALPPS feasible, there is scarcity of data in the literature to evaluate its outcome in comparison with open ALPPS with regard to perioperative recovery and liver regeneration. Hence, the aim of this project is to evaluate the short-term clinical outcomes of laparoscopic ALPPS and the impact of laparoscopy on liver remnant regeneration after ALPPS in a prospective randomised clinical trial setting.

Conditions

Liver Cancer

Keywords

ALPPS; Small future liver remnant; Liver cancer; Hepatocellular carcinoma; Liver metastasis; Laparoscopic surgery; Minimal invasive

Outcome Measures

Primary Outcomes (1)

• Amount of future liver remnant volume increment by percentage after stage I ALPPS

  Amount of future liver remnant volume increment by percentage after stage I ALPPS

  During hospital stay after stage I ALPPS, an average of 1-2 weeks

Secondary Outcomes (4)

• Preoperative blood loss during stage 1 ALPPS

  During hospital stay after stage I ALPPS, an average of 1-2 weeks

• Length of hospital stay after stage 1 ALPPS

  During hospital stay after stage I ALPPS, an average of 1-2 weeks

• Overall morbidity in number and mortality rates in percentage after stage 1 ALPPS

  During hospital stay after stage I ALPPS, an average of 1-2 weeks

• Inflammatory markers associated with inflammation and regeneration after stage 1 ALPPS

  During hospital stay after stage I ALPPS, an average of 1-2 weeks

Study Arms (2)

Laparoscopic ALPPS

EXPERIMENTAL

Laparoscopic ALPPS procedure

Procedure: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)

Open ALPPS

ACTIVE COMPARATOR

Open ALPPS procedure

Procedure: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)

Interventions

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) PROCEDURE

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a surgical procedure that induces rapid liver regeneration in patients with small liver remnant planning for major liver resection. It is a two-staged operation with stage I including portal vein ligation and splitting the right liver away from the left liver. After stage I, the left liver will undergo rapid liver regeneration and the stage II operation can be performed at 7-10 days after stage I operation when the liver remnant reaches an adequate size. In stage II operation, the right liver that contains the tumor is then removed.

Also known as: ALPPS

Laparoscopic ALPPS; Open ALPPS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis of malignant liver tumor contemplating for extended right hepatectomy or right trisectionectomy
• Patient consent
• Age \>/= 18
• FLR/ESLV \</= 30%
• Indocyanine green clearance rate at 15 mins : \< 18%
• Platelet count \> 100x10\^9/L
• Child A cirrhosis (due to hepatitis B/C virus, or alcohol, or autoimmune disease)
• American Society of Anaesthesiology score \< 3
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Technical factors eligible for laparoscopic ALPPS
• single long-segment portal

You may not qualify if:

• Absence of consent
• Decompensated liver disease as indicated by the presence of ascites, varices and hepatic encephalopathy
• ECOG performance status \>/= 3
• Main portal vein thrombosis
• FLR/ESLV \> 30%
• Technical factors not eligible for laparoscopic ALPPS
• Short-segment right portal vein or early bifurcation of right anterior/posterior portal vein, or other portal vein anomalies
• Large tumor size with diameter \> 5 cm
• Intolerance to CO2 pneumoperitoneum

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

Related Publications (11)

• Lang H, de Santibanes E, Schlitt HJ, Malago M, van Gulik T, Machado MA, Jovine E, Heinrich S, Ettorre GM, Chan A, Hernandez-Alejandro R, Robles Campos R, Sandstrom P, Linecker M, Clavien PA. 10th Anniversary of ALPPS-Lessons Learned and quo Vadis. Ann Surg. 2019 Jan;269(1):114-119. doi: 10.1097/SLA.0000000000002797.

  PMID: 29727331 BACKGROUND

• Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, Fichtner-Feigl S, Lorf T, Goralcyk A, Horbelt R, Kroemer A, Loss M, Rummele P, Scherer MN, Padberg W, Konigsrainer A, Lang H, Obed A, Schlitt HJ. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012 Mar;255(3):405-14. doi: 10.1097/SLA.0b013e31824856f5.

  PMID: 22330038 RESULT

• Schadde E, Ardiles V, Robles-Campos R, Malago M, Machado M, Hernandez-Alejandro R, Soubrane O, Schnitzbauer AA, Raptis D, Tschuor C, Petrowsky H, De Santibanes E, Clavien PA; ALPPS Registry Group. Early survival and safety of ALPPS: first report of the International ALPPS Registry. Ann Surg. 2014 Nov;260(5):829-36; discussion 836-8. doi: 10.1097/SLA.0000000000000947.

  PMID: 25379854 RESULT

• Linecker M, Bjornsson B, Stavrou GA, Oldhafer KJ, Lurje G, Neumann U, Adam R, Pruvot FR, Topp SA, Li J, Capobianco I, Nadalin S, Machado MA, Voskanyan S, Balci D, Hernandez-Alejandro R, Alvarez FA, De Santibanes E, Robles-Campos R, Malago M, de Oliveira ML, Lesurtel M, Clavien PA, Petrowsky H. Risk Adjustment in ALPPS Is Associated With a Dramatic Decrease in Early Mortality and Morbidity. Ann Surg. 2017 Nov;266(5):779-786. doi: 10.1097/SLA.0000000000002446.

  PMID: 28806301 RESULT

• Chan AC, Pang R, Poon RT. Simplifying the ALPPS procedure by the anterior approach. Ann Surg. 2014 Aug;260(2):e3. doi: 10.1097/SLA.0000000000000736. No abstract available.

  PMID: 24866543 RESULT

• Chan AC, Poon RT, Chan C, Lo CM. Safety of ALPPS Procedure by the Anterior Approach for Hepatocellular Carcinoma. Ann Surg. 2016 Feb;263(2):e14-6. doi: 10.1097/SLA.0000000000001272. No abstract available.

  PMID: 26079914 RESULT

• Raptis DA, Linecker M, Kambakamba P, Tschuor C, Muller PC, Hadjittofi C, Stavrou GA, Fard-Aghaie MH, Tun-Abraham M, Ardiles V, Malago M, Campos RR, Oldhafer KJ, Hernandez-Alejandro R, de Santibanes E, Machado MA, Petrowsky H, Clavien PA. Defining Benchmark Outcomes for ALPPS. Ann Surg. 2019 Nov;270(5):835-841. doi: 10.1097/SLA.0000000000003539.

  PMID: 31592812 RESULT

• Chan A, Zhang WY, Chok K, Dai J, Ji R, Kwan C, Man N, Poon R, Lo CM. ALPPS Versus Portal Vein Embolization for Hepatitis-related Hepatocellular Carcinoma: A Changing Paradigm in Modulation of Future Liver Remnant Before Major Hepatectomy. Ann Surg. 2021 May 1;273(5):957-965. doi: 10.1097/SLA.0000000000003433.

  PMID: 31305284 RESULT

• Machado MA, Makdissi FF, Surjan RC, Basseres T, Schadde E. Transition from open to laparoscopic ALPPS for patients with very small FLR: the initial experience. HPB (Oxford). 2017 Jan;19(1):59-66. doi: 10.1016/j.hpb.2016.10.004. Epub 2016 Nov 2.

  PMID: 27816312 RESULT

• Burpee SE, Kurian M, Murakame Y, Benevides S, Gagner M. The metabolic and immune response to laparoscopic versus open liver resection. Surg Endosc. 2002 Jun;16(6):899-904. doi: 10.1007/s00464-001-8122-x. Epub 2002 Feb 27.

  PMID: 12163951 RESULT

• Schlegel A, Lesurtel M, Melloul E, Limani P, Tschuor C, Graf R, Humar B, Clavien PA. ALPPS: from human to mice highlighting accelerated and novel mechanisms of liver regeneration. Ann Surg. 2014 Nov;260(5):839-46; discussion 846-7. doi: 10.1097/SLA.0000000000000949.

  PMID: 25379855 RESULT

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Albert Chan

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Albert Chan

CONTACT

+85222553025; acchan@hku.hk

Crystal Kwan

CONTACT

+85222556646; cryskal@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Model Details: Patient are randomly assigned into either open or laparoscopic approach. The ratio of open and laparoscopic is 1:1.

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: April 30, 2021
• Study Start: September 2, 2020
• Primary Completion: December 31, 2023
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)