Clinical trial NCT02164292: ALPPS: Safety, Feasibility and Efficacy at a Single Center
Official title: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Safety, Feasibility and Efficacy at a Single Center
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Locally Advanced Malignant Liver Disease
Keywords: Liver tumor
ALPPS
Two-stage hepatectomy
Morbidity
Hypertrophy
Lead sponsor: Hospital Italiano de Buenos Aires
Sponsor class: OTHER
First posted: 2014-06-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: High-Volume University Hospital population

Brief summary: The possibility to achieve a curative resection in patients with liver malignancies is limited by the future liver remnant (FLR). The Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) approach has recently been introduced as a revolutionary strategy to achieve resectability by inducing a rapid and large FLR hypertrophy. However, the possibility of achieving a short-term hypertrophy and high resectability rates has been counteracted in most published series by an increased risk of morbidity and mortality.The aim of this study was to evaluate the results with the ALPPS procedure in a single high-volume HPB center, with special emphasis in the safety and feasibility of this new 2-stage strategy. The aim of the present study was to assess the safety, feasibility and efficacy of ALPPS in a single high-volume hepatobiliary center.

Detailed description: Complete resection of liver malignancies remains as the best treatment to offer the possibility of long-term survival or cure. At diagnosis, many patients have locally advanced disease that often precludes a curative resection. During the past two decades, a better assessment of resectability through modern imaging techniques along with new multimodal therapies and the introduction of modern chemotherapy regimens have allowed to increase the pool of candidates for surgical treatment in patients with locally advanced disease. The current principles for safe liver resections focus mainly on the liver parenchyma that remains after resection rather than the liver resected. In fact, one of the main conditioning factors of posthepatectomy liver failure (PHLF) is the amount and quality of future liver remnant (FLR). The induction of hypertrophy of healthy parenchyma using either portal vein embolization (PVE) or ligation (PVL), in the setting of 1-stage or 2-stage liver resections, is nowadays considered the standard of care for patients with locally advanced liver tumors and small FLR.2,5-8 However, the need for long intervals between interventions (6-12 weeks), results in resectability rates that rarely exceed 60-80%.

In 2012, Schnitbauer et al introduced a novel 2-stage technique that allowed tumor resection in 25 patients from 5 German centers with marginally resectable or primarily nonresectable disease by means of a rapid and large FLR hypertrophy. This technique was later popularized with the acronym ALPPS for "Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy". The promising preliminary results obtained with this new surgical proposal in terms of hypertrophy and the possibility of challenging the previous methods generated a pronounced reaction in the surgical community world-wide that has rarely been seen in the history of hepato-pancreato-biliary (HPB) surgery. However, the possibility of achieving a short-term hypertrophy and high resectability rates has been counteracted in most published series by an increased risk of morbidity and mortality. The aim of this study was to evaluate the results with the ALPPS procedure in a single high-volume HPB center, with special emphasis in the safety and feasibility of this new 2-stage strategy.

Data for all patients undergoing 2-stage hepatectomies with the ALPPS approach at the HPB Surgery Section of the Hospital Italiano de Buenos Aires between June 2011 and April 2014 was analyzed on an intention to treat basis. Patient demographics, clinical characteristics (body mass index, anesthesiological risk score, Charlson comorbidity index, preoperative chemotherapy), tumor type, surgical details, FLR hypertrophy, postoperative liver function, postoperative complications, length of hospital stay and survival were analyzed.

Regarding the surgical procedure, during the first stage a complete tumor resection (clean-up) of the FLR is performed if bilateral disease was present, either trough anatomical or atypical resections. Subsequently, the portal vein of the diseased hemi-liver (DH) is divided and either total (up to the inferior vena cava) or partial (up to the middle hepatic vein) parenchymal transection using the Cavitron Ultrasonic Surgical Aspirator (CUSA; Valley Lab, Boulder, CO, USA) is carried out. At the end of the first stage, the DH is either wrapped in a plastic bag or a plastic sheath placed between the cut surfaces. Once volumetric CT analysis demonstrated enough FLR hypertrophy and provided the patient is in good condition, the second stage is carried out the next available operative day resecting the DH. The type of liver resections performed were defined using the Brisbane 2000 nomenclature.

Eligibility criteria: Inclusion Criteria:

* Patients with marginally resectable or primarily non-resectable locally advanced liver tumors
* Insufficient FLR either in volume or quality

Exclusion Criteria:

* Unresectable liver metastases in the future liver remnant or unresectable extrahepatic metastases
* Severe portal hypertension
* High anesthesiological risk
* Unresectable primary tumor

Primary outcomes:
measure: Safety of the procedure defined as the incidence of postoperative complications and mortality
timeFrame: within the first 90 days after the first stage
measure: Feasibility of the procedure defined as percentage of patients that complete both surgical stages.
timeFrame: within 4 months after the first stage
Secondary outcomes:
measure: Efficacy of the procedure defiend as the percentage of patients who achieve a sufficient future liver remnant hypertrophy
timeFrame: within 10 days after the first stage
measure: Disease-free survival and overall survival
timeFrame: 1 and 2 years
measure: Risk factors for morbidity
timeFrame: within 3 month after the first stage
measure: Risk factors for a reduced kinetic growth rate of the future liver remnant (<35 cc/day)
timeFrame: within 3 months after the first stage
Other outcomes:
Locations:
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Buenos Aires
Study officials:
affiliation: General Surgery Service, Hospital Italiano de Buenos Aires. Argentina
name: Eduardo de Santibañes, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Agrawal S, Belghiti J. Oncologic resection for malignant tumors of the liver. Ann Surg. 2011 Apr;253(4):656-65. doi: 10.1097/SLA.0b013e3181fc08ca.
citation: Clavien PA, Petrowsky H, DeOliveira ML, Graf R. Strategies for safer liver surgery and partial liver transplantation. N Engl J Med. 2007 Apr 12;356(15):1545-59. doi: 10.1056/NEJMra065156. No abstract available.
citation: Mise Y, Sakamoto Y, Ishizawa T, Kaneko J, Aoki T, Hasegawa K, Sugawara Y, Kokudo N. A worldwide survey of the current daily practice in liver surgery. Liver Cancer. 2013 Jan;2(1):55-66. doi: 10.1159/000346225.
citation: 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.
citation: de Santibanes E, Clavien PA. Playing Play-Doh to prevent postoperative liver failure: the "ALPPS" approach. Ann Surg. 2012 Mar;255(3):415-7. doi: 10.1097/SLA.0b013e318248577d. No abstract available.
citation: Shindoh J, Vauthey JN, Zimmitti G, Curley SA, Huang SY, Mahvash A, Gupta S, Wallace MJ, Aloia TA. Analysis of the efficacy of portal vein embolization for patients with extensive liver malignancy and very low future liver remnant volume, including a comparison with the associating liver partition with portal vein ligation for staged hepatectomy approach. J Am Coll Surg. 2013 Jul;217(1):126-33; discussion 133-4. doi: 10.1016/j.jamcollsurg.2013.03.004. Epub 2013 Apr 28.
citation: Schadde E, Ardiles V, Slankamenac K, Tschuor C, Sergeant G, Amacker N, Baumgart J, Croome K, Hernandez-Alejandro R, Lang H, de Santibanes E, Clavien PA. ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors compared with conventional-staged hepatectomies: results of a multicenter analysis. World J Surg. 2014 Jun;38(6):1510-9. doi: 10.1007/s00268-014-2513-3.
citation: Torres OJ, Fernandes Ede S, Oliveira CV, Lima CX, Waechter FL, Moraes-Junior JM, Linhares MM, Pinto RD, Herman P, Machado MA. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): the Brazilian experience. Arq Bras Cir Dig. 2013 Jan-Mar;26(1):40-3. doi: 10.1590/s0102-67202013000100009. English, Portuguese.