title: Resection of hepatocellular carcinoma in elderly patients and the role of energy balance.
abstract: BACKGROUND
  Progressive functional impairment with age has a significant impact on perioperative risk management. Chronic liver diseases induce a strong oxidative stress; in the elderly, in particular, impaired elimination of free radicals leads to insufficient DNA repair. The events associated with a weak response to growth factors after hepatectomy leads to a decline in liver regeneration. Hypercholesterolemia is highly prevalent in the elderly, which may alter the coenzyme Q10 (CoQ) levels and in turn the cellular energy balance. This condition is commonly treated with statins. The aim of this study is to investigate the role of preoperative cellular energy balance in predicting hepatocellular carcinoma (HCC) postresection outcomes.
  
  
  METHODS
  In a 5-year period (2009-2013), elderly patients with hypercholesterolemia, cardiovascular disease, and diabetes mellitus, undergoing HCC resection, were recruited and grouped by age (<75 and ≥ 75 years old). All patients were previously treated with statins. The risk factors associated with hospital morbidity/mortality and prolonged length of stay (LOS) were evaluated.
  
  
  RESULTS
  Forty-five elderly patients were recruited and grouped according to their treatment: Group 1 (n = 23) was treated with statins alone (control group), whereas Group 2 (n = 22) was treated with statins and a CoQ analogue, 3 weeks from the surgery and at least a month later (experimental group). The majority of our patients were treated with atorvastatin [n = 28 (53.84%)] and the minority with simvastatin [n = 17 (32.69%)], 20 mg/day, for at least 3 years before the surgery. Perioperative mortality was observed in one patient of Group 1 (4.3%). Morbidities were noted in 13 patients of Group 1 (56.5%) and four patients of Group 2 (18.2%). The control group showed delayed functional recovery, muscle weakness, increased infection rate, and pleural effusion due to prolonged bed rest (hospital stay 13 days (7-19) vs. 8.5 days (5-12)), compared with the experimental group. The overall survival at 5 years was similar for both groups (n = 10 patients (43%) in Group 1 vs. n = 10 patients (45%) in Group 2).
  
  
  CONCLUSIONS
  In the elderly population, survival is closely linked to postoperative morbidity and mortality. In our study, prolonged LOS was found to be related to delayed bioenergetic recovery. When limited, risk factors such as infections, neutropenia, and red blood cell transfusions could lower LOS and mortality of elderly patients with HCC. Higher age was associated with greater postoperative morbidity and successful hospital stay.
authors.affiliation: Department of Surgery, Annunziata Hospital of Cosenza, Cosenza, Italy. Electronic address: anubis_m@libero.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Cannistrà
authors.affiliation: Department of Medical and Surgical Sciences, University of Catanzaro, Italy. Electronic address: raffaele.eia@alice.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Grande
authors.affiliation: Department of Medical and Surgical Sciences, University of Catanzaro, Italy. Electronic address: ruggant@alice.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Ruggiero
authors.affiliation: Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Italy. Electronic address: matteo.novello@studio.unibo.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Novello
authors.affiliation: Department of Medical and Surgical Sciences, University of Catanzaro, Italy. Electronic address: alessandra.zullo@gmail.com.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zullo
authors.affiliation: Department of Surgery, Annunziata Hospital of Cosenza, Cosenza, Italy. Electronic address: bonaiutoelisabetta@gmail.com.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bonaiuto
authors.affiliation: Department of Surgery, Annunziata Hospital of Cosenza, Cosenza, Italy. Electronic address: s.vaccarisi@libero.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Vaccarisi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Italy. Electronic address: giuseppe.cavallari3@unibo.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cavallari
authors.affiliation: Department of Medical and Surgical Sciences, University of Catanzaro, Italy. Electronic address: rserra@unicz.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Serra
authors.affiliation: Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Italy. Electronic address: bruno.nardo@unibo.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Nardo
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000523:psychology / Q000601:surgery*; D005221:Fatigue / Q000209:etiology; D005260:Female; D006299:Health Services for the Aged; D006498:Hepatectomy / Q000009:adverse effects; D017052:Hospital Mortality; D006801:Humans; D007558:Italy; D007902:Length of Stay; D008113:Liver Neoplasms / Q000401:mortality / Q000523:psychology / Q000601:surgery*; D008297:Male; D011183:Postoperative Complications / Q000209:etiology; D011184:Postoperative Period; D012307:Risk Factors
keywords: Coenzyme Q10; Elderly patients; HCC; Liver failure; Statins