Background
Methods/design
Trial population
Inclusion criteria
Exclusion criteria
Study design
Randomization and blinding
Withdrawal
Ethics, study registration, and consent
Data management and quality assurance
Surgical interventions
Preoperative evaluation
Surgical procedures
Group A: liver resection with hepatic inflow occlusion
Group B: liver resection without hepatic inflow occlusion
Postoperative management
Follow-up
Endpoints
Primary endpoint
Secondary endpoints
Endpoints | Definition |
---|---|
Primary | |
Postoperative liver function | Serum TBil on POD 5 [26] |
Secondary | |
Procedural parameters | |
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) |
Perioperative serum parameters | |
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 |
Postoperative course | |
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. |
Long-term outcomes | |
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] |