Dataset Information

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

ABSTRACT:

Background

ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC).

Methods

The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis.

Results

One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC.

Conclusion

ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

SUBMITTER: Li J

PROVIDER: S-EPMC7138775 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

Li Jun J Moustafa Mohamed M Linecker Michael M Lurje Georg G Capobianco Ivan I Baumgart Janine J Ratti Francesca F Rauchfuss Falk F Balci Deniz D Fernandes Eduardo E Montalti Roberto R Robles-Campos Ricardo R Bjornsson Bergthor B Topp Stefan A SA Fronek Jiri J Liu Chao C Wahba Roger R Bruns Christiane C Brunner Stefan M SM Schlitt Hans J HJ Heumann Asmus A Stüben Björn-Ole BO Izbicki Jakob R JR Bednarsch Jan J Gringeri Enrico E Fasolo Elisa E Rolinger Jens J Kristek Jakub J Hernandez-Alejandro Roberto R Schnitzbauer Andreas A Nuessler Natascha N Schön Michael R MR Voskanyan Sergey S Petrou Athanasios S AS Hahn Oszkar O Soejima Yuji Y Vicente Emilio E Castro-Benitez Carlos C Adam René R Tomassini Federico F Troisi Roberto Ivan RI Kantas Alexandros A Oldhafer Karl Juergen KJ Ardiles Victoria V de Santibanes Eduardo E Malago Massimo M Clavien Pierre-Alain PA Vivarelli Marco M Settmacher Utz U Aldrighetti Luca L Neumann Ulf U Petrowsky Henrik H Cillo Umberto U Lang Hauke H Nadalin Silvio S

Annals of surgical oncology 20200130 5

<h4>Background</h4>ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC).<h4>Methods</h4>The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as ...[more]

PMID: 32002719

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Project description:BackgroundIntrahepatic Cholangiocarcinoma (iCCA) is characterized by a strong stromal reaction playing a role in tumor progression. Thymus cell antigen 1 (THY1), also called Cluster of Differentiation 90 (CD90), is a key regulator of cell-cell and cell-matrix interaction. In iCCA, CD90 has been reported to be associated with a poor prognosis. In an iCCA PDX model, we recently found that CD90 was downregulated in mice treated with the Notch γ-secretase inhibitor Crenigacestat. The study aims to investigate the role of CD90 in relation to the NOTCH pathway.MethodsTHY1/CD90 gene and protein expression was evaluated in human iCCA tissues and xenograft models by qRT-PCR, immunohistochemistry, and immunofluorescence. Notch1 inhibition was achieved by siRNA. THY1/CD90 functions were investigated in xenograft models built with HuCCT1 and KKU-M213 cell lines, engineered to overexpress or knockdown THY1, respectively.ResultsCD90 co-localized with EPCAM, showing its epithelial origin. In vitro, NOTCH1 silencing triggered HES1 and THY1 down-regulation. RBPJ, a critical transcriptional regulator of NOTCH signaling, exhibited putative binding sites on the THY1 promoter and bound to the latter, implying CD90 as a downstream NOTCH pathway effector. In vivo, Crenigacestat suppressed iCCA growth and reduced CD90 expression in the PDX model. In the xenograft model, Crenigacestat inhibited tumor growth of HuCCT1 cells transfected to overexpress CD90 and KKU-M213 cells constitutively expressing high levels of CD90, while not affecting the growth of HuCCT1 control cells and KKU-M213 depleted of CD90. In an iCCA cohort, patients with higher expression levels of NOTCH1/HES1/THY1 displayed a significantly shorter survival.ConclusionsiCCA patients with higher NOTCH1/HES1/THY1 expression have the worst prognosis, but they are more likely to benefit from Notch signaling inhibition. These findings represent the scientific rationale for testing NOTCH1 inhibitors in clinical trials, taking the first step toward precision medicine for iCCA.

Dataset Information

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

Background

Methods

Results

Conclusion

Publications

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

Similar Datasets

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