title: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) does not affect proliferation, apoptosis, or angiogenesis as compared to standard liver resection for colorectal liver metastases.
abstract: BACKGROUND
  ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a novel two-stage strategy to induce rapid hypertrophy of the future liver remnant (FLR) when patients are in danger of postoperative liver failure due to insufficient FLR. However, the effects of ALPPS on colorectal liver metastases (CRLM) are not clear so far. The aim of our study was to determine whether ALPPS induces proliferation, apoptosis, or vascularization compared to standard (one-stage) liver resection.
  
  
  METHODS
  Six patients who underwent ALPPS were matched with 12 patients undergoing standard liver resection regarding characteristics of the metastases (size, number), time of appearance (syn-/metachronous), preoperative chemotherapy, primary tumor (localization, TNM stage, grading), and patient variables (gender, age). The largest resected metastasis was used for the analyses. Tissue was stained for tumor cell proliferation (Ki67), apoptosis (TUNEL, caspase-3), vascularization (CD31), and pericytes (αSMA).
  
  
  RESULTS
  Vascularization (CD31; p = 0.149), proliferation (Mib-1; p = 0.244), and αSMA expression (p = 0.205) did not significantly differ between the two groups, although a trend towards less proliferation and αSMA expression was observed in patients undergoing ALPPS. Concerning apoptosis, caspase-3 staining showed significantly fewer apoptotic cells upon ALPPS (p < 0.0001), but this was not confirmed by TUNEL staining (p = 0.7344).
  
  
  CONCLUSIONS
  ALPPS does not induce proliferation, apoptosis, or vascularization of CRLM when compared to standard liver resection.
authors.affiliation: Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Joechle
authors.affiliation: Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Moser
authors.affiliation: Department of Pathology, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Ruemmele
authors.affiliation: Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Schmidt
authors.affiliation: Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Werner
authors.affiliation: Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.affiliation: Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.affiliation: Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany. sven.lang@ukr.de.
authors.forename: Sven A
authors.initials: SA
authors.lastname: Lang
mesh_terms: D000368:Aged; D017209:Apoptosis; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D006984:Hypertrophy; D008026:Ligation; D017093:Liver Failure / Q000517:prevention & control; D008113:Liver Neoplasms / Q000098:blood supply / Q000556:secondary / Q000601:surgery*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011169:Portal Vein / Q000473:pathology / Q000601:surgery*; D011379:Prognosis
keywords: Apoptosis; Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS); Colorectal liver metastases (CRLM); Proliferation; Vascularization