Comparison of Hydro-dissection Versus Ultrasonic Aspirator in Division of Liver Parenchyma in Laparoscopic Resection
Phase: NA
Conditions: Liver Transection During Laparoscopic Liver Resection
Sponsor: Moscow Clinical Scientific Center

Comparison of hydro-dissection versus 
ultrasonic aspirator in division of liver 
parenchyma in laparoscopic resection 
 
 
 
Lap Liver Study 
 
 
 
NCT03208192 
 
 
 
20/02/2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Design – Lap Liver Resection 
 
 
Title of the study: comparison of water-jet dissector with ultrasonic aspirator in division of liver 
parenchyma in laparoscopic resection  
 
Background: until now, there is no agreement about the safest and feasible method for liver 
parenchyma transection during laparoscopic liver resection. 
Study design: prospective, randomized, single-center 
The purpose of the study: comparison of short-term results of two methods of parenchyma liver 
transection during laparoscopic liver resection 
 
Material and Methods: two groups will be compared. 
Group 1: liver resection using a bipolar dissector (Erbe), ultracision harmonic scalpel (Ethicon) 
and water-jet dissector (ERBEJET 2). 
Group 2: liver resection using a bipolar dissector (Erbe), ultracision harmonic scalpel (Ethicon), 
and ultrasonic aspirator (Misonix/SonaStar Ultrasonic Surgical Aspiration System) 
 
Indication laparoscopic liver resection. 
 Benign liver tumors (hemangioma, focal nodular hyperplasia, hepatocellular adenoma, 
biliary cystadenoma):  
o lesions of 7 cm or more and clinical manifestation with complaints of abdominal 
pain due to physical activity or body position. 
o Unresolved suspicion for malignancy  
 Hydatid echinococcosis   
 Malignant tumors (colorectal cancer metastases in the liver, hepatocellular carcinoma, 
intrahepatic cholangiocellular carcinoma, gallbladder cancer T1b-3NxM0  
 
For enlargement of the groups patients with Hydatid echinococcosis are included if total 
pericystectomy is performed. The surgery in those cases does not differ from liver resection for 
benign tumors. 
 
Inclusion Criteria:  
 Patients with benign lesions (hemangioma, focal nodular hyperplasia [FNH], 
hepatocellular adenoma, biliary cystadenoma, hydatid echinococcosis [only with total 
pericystectomy]) and malignant tumors (colorectal cancer metastases in the liver 
[CRLM], hepatocellular carcinoma [HCC], intrahepatic cholangiocellular carcinoma, 
gallbladder cancer T1b-3NxMo without invasion into bile ducts and adjacent organs), 
which involves laparoscopic segmental or major resection of the liver.  
 Gender: both, male and female 
 Minimum age 18 years 
 Maximum age: 80 years  
 ASA physical status I-IV 
 BMI up to  40 kg/m2 
 No simultaneous extrahepatic intra-abdominal procedures (bile duct resection, colon 
resection, partial duodenum resection) 
 Total bilirubin up to 100mmol/l if jaundice presents in non-cirrhotic patients 
 If cirrhosis is present, class A and B according to CTP score 
 
Exclusion Criteria 
 Difficulty index > 12 points (see below) 

 Tumor invasion of IVC or portal trunk (necessity of vascular reconstruction)  
 Repeated liver resection before laparoscopic resection (the single resection before is not a 
contraindication)  
 Simultaneous extra-hepatic intra-abdominal procedures (bile duct resection, colon 
resection etc.) 
 Age under 18 years  
 Age above 80 years  
 ASA physical status >IV 
 BMI > 40 kg/m2 
 Total bilirubin >100mmol/l if jaundice presents in non-cirrhotic patients 
 If cirrhosis is present, class C according to CTP score 
 Persons who are incapable of giving consent 
 Pregnant or breast-feeding women 
 Patients enlisted in other studies  
 
 
Preoperative examination:  
1. Hematology (WBC, RBC, Hb, Plt) 
2. Biochemistry (CRP, TP, AST, ALT, total bilirubin, creatinine, glucose)  
3. Abdominal ultrasound examination (tumor location, size and involvement of large 
vessels)  
4. Abdominal enhanced CT (with or without MRI) (tumor location, size and involvement of 
large vessels)  
5. Chest CT  
6. The upper digestive tract endoscopic examination  
 
Additional examination for patients with malignant tumors:  
7. Colonoscopy (if last procedure >1year)   
8. Tumor markers (CEA and CA 19-9 for CRLM, AFP and CA 19-9 for primary liver 
tumors). 
 
Postoperative examination. 
Further evaluation will be done at PO Day 2, 4, 6, 28. On Day 7 some patients may be 
discharged.  
If patient stays in hospital more than 30 days, evaluation (hematology, biochemistry and US 
examination) on PO Week 2, 3, 4 and 5 until discharge will be done. Abdominal CT should be 
undertaken if needed. 
 
1. Hematology (WBC, RBC, Hb, Plt) 
2. Biochemistry (CRP, TP, AST, ALT, total bilirubin, creatinine, glucose)  
3. Abdominal ultrasound examination (fluid collections and liver ischemia with estimation 
of the size and localization, pleural effusion with estimation of side and volume) 
 
Difficulty Index 
It is mandatory to estimate the complexity of laparoscopic liver resection by calculating the 
difficulty index proposed by Go Wakabayashi (2014) and modified in 2016 (attachment 1).  
As the difficulty index includes the type of liver resection (partial resection, segmentectomy, and 
sectionectomy), the size and topography of the tumor, its proximity to the large vessels of the 
liver, the presence and stage of liver cirrhosis (CTP), all patients in each group will be divided 
into four subgroups according to the complexity of liver resection: low, intermediate, advanced 
and expert. 
The comparison will be conducted between groups 1 and 2 according to difficulty of liver 

resection. 
 
Comparative analysis should include following intraoperative and postoperative factors 
 
Primary endpoint:  
Intraoperative blood loss - absolute measurement of blood loss in relation to resection size 
(ml/cm2) 
Absolute blood loss will be calculated as the amount of blood (collected only during the 
parenchyma resection) in suction the container after the subtraction of all irrigating fluids and 
weighing operative sponges.  
 
Secondary endpoints:  
Intraoperative factors:  
1. Blood loss relative to total blood volume (%) (attachment 2) 
2. Duration of liver parenchyma transaction. 
3. Necessity to apply the Pringle maneuver.  
4. Number of Pringle maneuver applications. 
5. The total duration of Pringle maneuver. 
6. Duration of the longest application of Pringle maneuver 
7. Number of patients needed for banked blood transfusion 
8. Number of bank blood units needed for transfusion  
9. Rate of conversion to hybrid (with upper midline incision of 10 cm long), open or robotic 
surgery 
10. Open/lap surgery before laparoscopic procedure 
 
Postoperative factors:  
1. Morbidity according to Clavien-Dindo classification (it is advisable to activate 
complications class II-V), as shown in attachment 3.  
2. Duration of hospital stay 
 
Bile leakage will be classified in severity according to the international study group for liver 
surgery (A,B,C) (attachment 4). 
 
Since the difficulty index does not take into account the number of liver lesions (and, in fact, 
needs to be calculated for each of the multiple lesions), only resection of the liver lesion with the  
highest difficulty index must be considered when comparing groups (especially for the liver 
parenchyma transection).  
 
Flow chart and CRF are attached.  
 
The number of patients in each group requires revision in line with the required statistical 
power of the study. Most likely, it requires at least 50 patients in each group (total number – not 
less than 100 patients).  
 
 
Mikhail Efanov, MD, PhD, 
Head of the HepatoPancreatoBiliary 
Surgery Department, 
Moscow Clinical Scientific Center 
+7(916) 105-88-30 
www.mknc.ru 
 

Attachment 1 
Difficulty index score (IWATE Criteria) 
 
 
Source:  
Wakabayashi G. What has changed after the Morioka consensus conference 2014 on 
laparoscopic liver resection? Hepatobiliary Surg Nutr. 2016 5(4):281-89 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960417/ 
 
Attachment 2 
 
Patient-specific relative blood loss (RBL %) was calculated as follows:  
RBL (%) = [intraoperative blood loss (mL) / estimated blood volume (mL)] x 100 
 
Calculation of Total Blood Volume by Nadler’s equation. 

The average blood volume is calculated as 75 ml/kg for men and 65 ml/kg for women, and in case of 
obesity 70 ml/kg for men and 60 ml/kg for women. 
 
Source:  
Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery 
1962;51:224–32 
http://www.surgjournal.com/article/0039-6060(62)90166-6/abstract 
 
Iijima T, Brandstrup B, Rodhe P, Andrijauskas A, Svensen CH. The maintenance and monitoring of 
perioperative blood volume. Perioper Med 2013;2:1–12. 
https://www.ncbi.nlm.nih.gov/pubmed/24472160 
 
 
Attachment 3 
 
CLAVIEN-DINDO GRADING SYSTEM FOR THE CLASSIFICATION OF  
SURGICAL COMPLICATIONS 
 
 Grades  
Definition  
Grade I:  
Any deviation from the normal postoperative course without the need for 
pharmacological treatment or surgical, endoscopic and radiological 
interventions.  
Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, 
analgetics, diuretics and electrolytes and physiotherapy. This grade also 
includes wound infections opened at the bedside.  
Grade II:  
Requiring pharmacological treatment with drugs other than such allowed for 
grade I complications. Blood transfusions and total parenteral nutrition are 
also included.  
Grade III:  
Requiring surgical, endoscopic or radiological intervention  
Grade III-a:  
Intervention not under general anesthesia  
Grade III-b:  
Intervention under general anesthesia  
Grade IV:  
Life-threatening complication (including CNS complications: brain 
haemorrhage, ischaemic stroke, subarachnoid bleeding, but excluding 
transient ischaemic attacks) requiring IC/ICU management.  
Grade IV-a:  
Single organ dysfunction (including dialysis)  
Grade IV-b:  
Multi-organ dysfunction  
Grade V:  
Death of a patient  
Suffix 'd':  
If the patients suffers from a complication at the time of discharge, the suffix 
“d” (for ‘disability’) is added to the respective grade of complication. This 
label indicates the need for a follow-up to fully evaluate the complication  
 
Source:  
Dindo D., Demartines N., Clavien P.A.; Ann Surg. 2004; 244: 931-937 
http://www.surgicalcomplication.info/index-2.html 
 
 

Attachment 4 
A definition and grading of severity of bile leakage by the International Study Group of Liver 
Surgery 
 
Definition:  
Bile leakage is defined as bilirubin concentration in the drain fluid at least 3 times the serum 
bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative 
intervention resulting from biliary collections or bile peritonitis.  
 
Grading:  
 Grade A bile leakage causes no change in patients’ clinical management.  
 A Grade B bile leakage requires active therapeutic intervention but is manageable 
without relaparotomy.  
 Grade C bile leakage, relaparotomy is required. 
 
 
Source:  
Koch et al, Bile leakage after hepatobiliary and pancreatic surgery: A definition and grading of 
severity by the International Study Group of Liver Surgery. Surgery Volume 149, Issue 5, May 
2011, pages 680-688 
http://www.sciencedirect.com/science/article/pii/S0039606010006781