Biological Substrate of the Rapid Volumetric Changes Observed in the Human Liver During the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Approach.
BACKGROUND
The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) strategy induces rapid future liver remnant (FLR) hypertrophy. Hepatocyte cellular and molecular changes associated with liver hypertrophy during ALPPS remain ill-defined in humans.


METHODS
Patients undergoing the ALPPS approach between June 2011 and October 2014 were extracted. Biopsies from the FLR were obtained during the first and second stages. Hematoxylin-eosin staining and immunohistochemical analysis for expression of the proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were performed. The proliferative index was defined as: PCNA-TUNEL ratio.


RESULTS
Eleven of 34 patients treated were studied during both stages. Median FLR hypertrophy was 104 % in 6 days, with a mean difference between preoperative and postoperative volume of 361 ml (P < 0.001). The mean hepatocyte number increased from 52.7 cells/mm(2) in the first stage to 89.6 cells/mm(2) in the second stage (P = 0.001). PCNA expression increased by 190 % between stages with a linear correlation (r = 0.58) with macroscopic hypertrophy. The proliferative index increased from -3.78 cells/mm(2) in first stage to 2.32 cells/mm(2) in the second stage (P = 0.034).


CONCLUSIONS
The results of the present study indicate that the rapid FLR volumetric increase observed in ALPPS is accompanied by histological and molecular features of hepatocyte cell proliferation.
Department of General Surgery, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina. martin.desantibanes@hospitalitaliano.org.ar.
Martin
M
de Santibañes
Department of General Surgery, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina.
Agustin
A
Dietrich
Department of General Surgery, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina.
Fernando A
FA
Alvarez
Department of General Surgery, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina.
Victoria
V
Ardiles
Institute of Basic Science and Experimental Medicine (ICBME), Hospital Italiano de Buenos Aires, Potosí 4240, Buenos Aires, Argentina.
Monica
M
Loresi
Institute of Basic Science and Experimental Medicine (ICBME), Hospital Italiano de Buenos Aires, Potosí 4240, Buenos Aires, Argentina.
Maximiliano
M
D'adamo
Department of General Surgery, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina.
Eduardo
E
de Santibañes
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects* / Q000379:methods; D022781:Hepatocytes / Q000473:pathology; D006529:Hepatomegaly / Q000209:etiology*; D006801:Humans; D006984:Hypertrophy / Q000209:etiology; D008026:Ligation; D008113:Liver Neoplasms / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000601:surgery
Future liver remnant; Hypertrophy; Immunohistochemical analysis; Liver failure; Two stage hepatectomy