Table 1 Definition of endpoints

 Postoperative liver function

Serum TBil on POD 5 [26]

  Intraoperative blood loss

Total blood loss from skin incision to closure, including the amount of blood in the suction containers and the weight of absorptive materials after subtracting the rinse fluid and ascites

  Requirement of blood transfusion

Indication: massive hemorrhage (>1500 ml) or hemoglobin level <7 g/dl; amount of transfusion

  Liver transection time

Time from parenchymal dissection to removal of liver specimen (minutes)

  Operative time

Time from skin incision to closure (in minutes)

  Liver function

Serum ALT, AST, ALB, PT, and INR preoperatively and on PODs 1, 3, 5, and 7

  Inflammatory response

Serum TNF-α, IL-1α, IL-2, IL-6, IL-8, IL-10, PCT, and CRP preoperatively and on PODs 1, 3, 5, and 7

  Complications

Defined by Clavien-Dindo classification (I–IV) [27]

   PHLF

Increased INR (or need of clotting factors to maintain normal INR) and hyperbilirubinemia on or after POD 5; if INR or serum bilirubin concentration is increased preoperatively, PHLF is defined by increasing INR and bilirubin concentration on or after POD 5 (biliary obstruction should be ruled out); graded according to ISGLS [26] as follows:

A: PHLF requiring no or little change in patient’s clinical management

B: PHLF resulting in deviation from regular clinical management but manageable without invasive treatment

C: PHLF requiring invasive treatment

   Bile leakage

Increased bilirubin concentration (at least three times greater than the serum level measured at the same time) in abdominal drain or intraabdominal fluid on or after POD 3, or as need for radiological intervention (e.g., interventional drainage) because of biliary collections or relaparotomy resulting from bile peritonitis; graded according to ISGLS [39] as follows:

A: Bile leakage requiring no or little change in patient’s clinical management

B: Bile leakage requiring change in patient’s clinical management (e.g., additional diagnostic or interventional procedures) but manageable without relaparotomy, or a grade A bile leakage lasting >1 week

C: Bile leakage requiring relaparotomy

   Posthepatectomy hemorrhage (PHH)

Evidence of intraabdominal bleeding such as frank blood loss via the abdominal drains (e.g., hemoglobin level in drain fluid >3 g/dl) or detection of intraabdominal hematoma or active hemorrhage by abdominal imaging (ultrasound, CT, angiography); graded according to ISGLS [40] as follows:

A: PHH requiring transfusion of ≤2 U of PRBCs

B: PHH requiring transfusion of >2 U of PRBCs but manageable without invasive intervention

C: PHH requiring radiological interventional treatment (e.g., embolization) or relaparotomy

   Intraperitoneal effusion/abscess

Any imaging-detected intraperitoneal fluid collection and/or elevation of infectious parameters (CRP >2 mg/dl and/or leukocytes >100,000/ml), positive physical signs, and bacteriology of abdominal drainage

   Pulmonary infection

Elevation of infectious parameters (CRP >2 mg/dl and/or leukocytes >100,000/ml) and/or evidence of pulmonary infiltration on chest x-ray requiring antibiotic therapy

  Postoperative ICU/hospital stay

Time from day of operation through discharge from ICU and/or hospital (days)

  Total in-hospital expenditure

Costs from admission to discharge (¥/$)

 Mortality

In-hospital death and 90-day death.

  Survival

1-, 3-, and 5-year overall and disease (tumor)-free survival

  Tumor recurrence

Identification of the typical hallmarks of recurrent HCC foci by dynamic imaging (CT/MRI) plus AFP >400 ng/ml in suboptimal settings (e.g., foci <2 cm) [24]