Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Cheng, 2022

Type of study: single-center retrospective analysis

Setting and country: China

Funding and conflicts of interest: none

Inclusion criteria:

All patients underwent radiofrequency ablation (RFA) or laparoscopic liver resection (LLR) for small HCC (defined as BCLC stage 0 or A, sized ≤3 cm, ≤3 nodules on contrast CT scan or MRI with no evidence of macrovascular invasion) from April 2005 to August 2020 were included.

Exclusion criteria:

n.a.

N total at baseline:

Intervention: 99

Control: 69

N total after matching:

I: 99

C: 31

Important prognostic factors²:

Age ± SD:

I: 63.60 ±9.86

C: 65.48±11.73

Number of tumors (1):

I: 97.0%

C:90.3%

Tumor size (cm)

I: 2.31 ±1.93

C: 1.14±0.70

Sex:

I: 82.8% M

C: 71.0% M

Describe intervention

For LLR, a 12-mm camera trocar was inserted at the subumbilical region, and 4–5 trocars of diameter 5–12 mm were used by the surgeon and assistant. Ultrasonic shear device or Cavitron Ultrasonic Surgical Aspirator (CUSA) was used to conduct liver parenchymal transection. Pringle maneuvers were employed selectively. Anatomical liver resection was defined as removal of the whole hepatic segment or subsegments supplied by the tumor bearing tributaries.

Describe  control

RFA were performed percutaneously using the Cool-tipTM RF Ablation System (Medtronic, USA) under local anesthesia. The RFA electrode was inserted under non-contrast ultrasound or CT scan guidance, with an intended ablative margin of at least 1 cm. Drain was placed only when clinically indicated.

Length of follow-up:

Median follow-up was 34 months (range, 1–175 months).

Loss-to-follow-up:

I: none

C: none

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

All complications:

I: 12.1%

C: 6.5%

(p= 0.374)

Major (Clavien-Dindo grade 3 or above) complications,

I: 1.0%

C: 0.0%
(p=0.574)

The LLR group and RFA group had similar overall survival rate (91.8% versus. 79.2% at 5-year, P=0.060); while the LLR group had a significantly better disease-free survival rate (49.0% versus. 30.3% at 5-year, P=0.002) and local recurrence-free rate (96.0% versus. 63.7% at 5-year, P<0.001) when compared with the RFA group.

In general, liver resection was first considered in all cases.

All LLR and RFA were performed by the same team of hepatobiliary surgeons and interventional radiologists respectively.

1:3 propensity score matching was conducted to match patients in the LLR group and RFA group. Prognostic indicators, i.e., age, gender, tumor size, tumor number, Child’s grading, albumin, bilirubin, platelet count, international normalized ratio, alpha-fetoprotein level and presence of cirrhosis on imaging were chosen for propensity score calculation.

The analysis was carried out on an intention-to-treat basis.

This study showed that both procedures were safe and feasible. RFA had a shorter hospital stay, while LLR had a lower local recurrence rate and better disease-free survival rate. Nevertheless, the overall survival was comparable between the two groups.

Magistri, 2020

Type of study: retrospective cohort analysis

Setting and country: Italy

Funding and conflicts of interest: none

Inclusion criteria:

All consecutive patients treated by robotic liver

resection (RLR) or percutaneous ablation) PA between January 2014 and October 2019 for a newly

diagnosed single HCC, less than 3 cm in size (very early/early stages according to Barcelona Clinic Liver Cancer (BCLC) on chronic

liver disease or liver cirrhosis

Exclusion criteria:
Patients with exophytic

lesions, tumors close the hepatic hilum or major hepatic veins, and nodules undetectable by US were

excluded from this analysis.

N total at baseline:

Intervention: 24

Control: 36

N total after matching:

I:

C:

Important prognostic factors²:

Age (range:

I: 64 (48-79)

C: 67 (20-87)

Number of tumors (1):

I: 100%

C: 100%

Tumor size (cm)

I: 2.0 (1.0–3.0)

C: 1.95 (1.2–3.0)

Charlson Comorbidity Index
I: 7

C: 7

Sex:

I: 67% M

C: 72% M

Describe intervention

The RLR included 16 wedge resections and 8 segmentectomies, performed with or without

intermittent hilar clamping (Pringle maneuver was performed in three cases: total clamping interval of

32, 50, and 72 min, respectively) and using a combination of monopolar energy, bipolar energy, and da

Vinci Harmonic ACE for parenchymal transection.

Describe  control

All patients were placed under conscious sedation, and the procedure was carried out under

local anesthesia with ultrasonographic guidance. Three senior interventional radiologists performed

the procedures.

Percutaneous RFA was performed using a

StarBurst XL–Electrosurgical Device

(AngioDynamics Inc., Latham, NY, USA), which is a single electrode placed centrally within the HCC

nodules. The radiofrequency is usually emitted for 10 to 15 min at 100W; timing and energy varies

according to the tumor size and location. The ablation process may be repeated to obtain an entire

treated area of at least 1 cm around the edges of the nodule.

Percutaneous MWA was performed using a Solero–Microwave Tissute Ablation Applicator

(AngioDynamics Inc., Latham, NY, USA) for 3–6 min at 60–80 W; timing and the energy issued varied

according to the tumor size and location.

MWA is preferred when the lesion is close to a vessel at the preprocedural ultrasound study.

In fact, MWA is related to a reduced heat “sink e
ect” compared to RFA.

Length of follow-up:
The median follow-up time was 29 months (range 11–38) in the RLR group and 22 months (range 13–32) in the PA group.

Loss-to-follow-up:

I: none

C: none

Incomplete outcome data:

Outcome measures and effect size (include 95%CI and p-value if available):

All complications:

I: 38% 

C: 19%
(p=0.34)

Major (Clavien-Dindo grade 3 or above) complications,

I: 4%

C: 3%

Liver failure

I: 4%

C: 0%

(p=0.40)

All HCC patients were discussed by multidisciplinary board.

RLRs were performed using the da Vinci Si robotic platform (Intuitive Surgical inc.,

Sunnyvale, CA, USA) by the same surgeon.
No intraoperative complications or

deaths occurred.

Zhang, 2020

Type of study: retrospective analysis

Setting and country: China

Funding and conflicts of interest: none

Inclusion criteria:

Patients with small HCC (<2,0 cm) in a hospital from July 2016 to July 2019

Exclusion criteria: n.a.

N total at baseline:

Intervention: 85

Control: 90

N total after matching:

I:

C:

Important prognostic factors²:

Age± SD:

I: 63.5±7.6

C: 62.8±8.5

Number of tumors (1):

I: 74.1%

C: 91.2%

TNM stage I

I: 71.8%

C:93.3%

Sex:

I: 55% M

C: 52% M

For hepatic/laparoscopic resection (HR), patients were placed under general anaesthesia, a 1 cm sub-umbilical incision

was made, and a trocar with a diameter of 1 cm was inserted to determine the location

of the tumour. The hepatic ligament was then removed and labelled on the surface of

the liver 2 cm adjacent to the tumour. Finally, we completely resected the entire

hepatic segment or lobe.

For percutaneous radiofrequency ablation (PRFA) For PRFA we used computed tomography (CT) or magnetic

resonance imaging (MRI) for ultrasonography guidance in real-time. We intercostally

or subcostally inserted a 17-gauge cooled-tip electrode of 2–3 cm. The ablation

procedures generally lasted 12 min with a 3 cm electrode and 6 min with a 2 cm

electrode, and a power of 80 W–100 W was typically used. The lesions were assessed

one and eight weeks after PRFA by CT or MRI

Length of follow-up:
2.0 ± 0.5-year

Loss-to-follow-up:

I: n.a.

C: n.a

Incomplete outcome data: n.a.

Outcome measures and effect size (include 95%CI and p-value if available):

Complications:

I: 20%

C: 7.78%

(p=0.033)

Liver failure

I: 1.18%

C: 0%

(p=0.977)

PRFA treatment

reduced the incidence of complications compared with resection and significantly

improved overall survival as well as recurrence-free survival.

A higher proportion of patients who received HR had

liver cirrhosis and multiple tumours (C2) and exhibited higher TNM stages compared

with patients who received PRFA.

During the follow-up period, the patients were followed up by CT or MRI examinations every 3–4 mo in the first two years after PRFA treatment.

Ding, 2022

Type of study: retrospective analysis

Setting and country: China

Funding and conflicts of interest: none

HCC patients from September 1, 2013 to June 30, 2019.

Inclusion criteria:

(a) a diagnosis of HCC with pathological confirmation; (b) Barcelona Clinic Liver Cancer stage 0-A; (c) no treatment history; and (d) more than 6 months of follow-up.

Exclusion criteria:  (a) combined MWA or RFA during RH; (b) palliative treatment; and (c) switching from RH to open surgery during the operation (these patients were counted as RH failure cases but were not included in the final analysis).

N total at baseline:

Intervention: 161

Control: 240

N total after matching:

I: 122

C 122

Important prognostic factors²:

Age± SD:

I: 58.94±10.21

C: 58.61±11.25

Tumor size (cm)

I: 2.94±1.12

C: 2.85±1.07

Multiple tumor

I: 6.6%

C: 4.1%

Charlson Comorbidity Index 0
I: 62.3%

C: 59%

Sex:

I: 83.6%M

C:  85.2%M

Robot-assisted hepatectomy (RH),

Da Vinci system was used for all operations in the RH group. When bleeding could not be controlled or the tumor could not be removed by RH, the treatment was switched from RH to open surgery

Microwave ablation (MWA)

All patients in the MWA group underwent tumor puncture biopsy before treatment and enhanced MRI within 3 days after ablation to observe the ablation zone and blood supply in surrounding areas. If the ablation zone was insufficient or abnormal blood perfusion occurred around the ablation zone, these patients received re-ablation to ensure sufficient tumor inactivation.

Length of follow-up:
28 months

Loss-to-follow-up:

I: n.a.

C: n.a.

Incomplete outcome data: n.a.

Outcome measures and effect size (include 95%CI and p-value if available):

Complications (within 90 days after treatment)

Total

I: 30.3%

C: 32%

(p=0.89)

Minor (Clavien-Dindo grade II):

I: 9.8%

C: 4.1%

(p=0.13)

Severe (Clavien-Dindo grade III-V):

I: 2.5%

C: 0.8%

(p=0.61)

Severe complication (≥grade III) rates were minuscule and comparable in both groups, which meant that both RH and MWA had extremely high safety. However, the causes of complications in the two groups were different. Complications in the RH group were mainly caused by general anesthesia or massive blood transfusion, while in the MWA group, the cause of complications was mainly due to the puncture process.

no significant difference in total complications, minor complications or severe complications between the two groups in the crude, matched, or weighted cohort

1:1 propensity score matching was adopted to adjust baseline imbalances of preoperative clinical factors between the two groups.

Clinical and laboratory parameters of patients were retrieved from the hospital database.

Conticchio, 2021

Type of study: multicentric retrospective study

Setting and country: Europe (France; Spain; Switzerland; Italy)

Funding and conflicts of interest: none

Inclusion criteria: Patients who underwent Laparoscopic liver resection (LLR)

 or radiofrequency ablation (RFA) between 2009 and 2019. Only Child-Pugh class A and B patients aged ≥70 years who had a single HCC with a ≤3 cm diameter, without any evidence of major portal/hepatic vein branch invasion and extrahepatic disease.

N total at baseline:

Intervention: 86

Control: 98

N total after matching:

I: 58

C: 58

Important prognostic factors²:

Age (range):

I: 75.4 (69.5–86.5)

C: 74 (70–87)

Tumor size (cm)

I: 3.0 (1.0–3.0)

C: 2.0 (1.2–3.0)

Comorbidities >2
I: 40%

C: 60%

Sex:

I: 76%M

C:  64%M

The surgical strategy was tailored based on tumor size, position, and liver function. The type of liver resection was defined according to the Brisbane Classification.7 Trocars position and size were based on tumor location. Intraoperative ultrasonography was used routinely. Liver parenchymal transection was performed with various advanced instruments such as the laparoscopic cavitation ultrasonic surgical aspirator ultrasonic, bipolar, and integrated energy devices. Minor resection was defined as the resection of two or fewer Couinaud’s liver segments, and major resection was defined as the resection of three or more liver segments. Pringle’s maneuver was used during hepatectomy to control intraoperative bleeding. The specimen was placed in an endobag and extracted from one of the trocars’ introduction sites.

RFA was performed using an internally cooled electrode. Depending on the tumor size and position, either a single or clustered electrode was used for ablation under ultrasound guidance, either percutaneously or using a laparoscopic or an open approach. The procedure was performed under local anesthesia and intravenous sedation for percutaneous ablation, and general anesthesia was used for laparoscopic and open ablations.

Length of follow-up:
n.a.

Loss-to-follow-up:

I: n.a.

C: n.a.

Incomplete outcome data: n.a.

Outcome measures and effect size (include 95%CI and p-value if available):

Complications (within 90 days after treatment)

Total

I: 30.3%

C: 32%

(p=0.06)

Minor (Clavien-Dindo grade I-II):

I: 91%

C: 100%

Severe (Clavien-Dindo grade III-V):

I: 9%

C: 0%

Liver failure:

I: 10%

C: 2%

(p=0.11)

The complication rate is similar in both therapeutic strategies.

The type of treatment was planned in multidisciplinary team discussions including surgeons, hepatologists, oncologists, interventional radiologists, and pathologists.

Nodules with a median size of 30 mm, located in anterolateral segments,2–6 and in contact with Glissonian pedicles represent an indication for the laparoscopic approach.

1:1 propensity score matching was performed to decrease selection bias by building a matched group of patients. Variables entered in our propensity model included age, comorbidities 2, ASA score, BMI, Child-Pugh and MELD scores, and the presence of ascites or portal hypertension.

Author, year

Selection of participants

Was selection of exposed and non-exposed cohorts drawn from the same population?

Exposure

Can we be confident in the assessment of exposure?

Outcome of interest

Can we be confident that the outcome of interest was not present at start of study?

Confounding-assessment

Can we be confident in the assessment of confounding factors? 

Confounding-analysis

Did the study match exposed and unexposed for all variables that are associated with the outcome of interest or did the statistical analysis adjust for these confounding variables?

Assessment of outcome

Can we be confident in the assessment of outcome?

Follow up

Was the follow up of cohorts adequate? In particular, was outcome data complete or imputed?

Co-interventions

Were co-interventions similar between groups?

Overall Risk of bias

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Low, Some concerns, High

Cheng, 2022

Definitely yes

Definitely yes

Probably yes

Definitely yes

Definitely yes

Probably yes

Probably yes

Probably no

Low

Magistri, 2020

Probably yes

Probably yes

Probably yes

Probably yes

Probably no

Probably yes

Probably yes

Probably yes

Some concerns

Zhang, 2020

Probably yes

Probably yes

Probably yes

Probably yes

Probably no

Probably yes

Probably yes

Probably yes

Some concerns

Ding, 2022 

Definitely yes

Definitely yes

Probably yes

Definitely yes

Definitely yes

Probably yes

Probably yes

Probably yes

Low

Conticchio, 2021

Definitely yes

Probably yes

Probably yes

Definitely yes

Definitely yes

Probably yes

Probably yes

Probably yes

Low