Abstract
Background:
Laparoscopic anatomical liver resection of segment 8 (LALR-S8) remains a challenge for anatomical laparoscopic segmentectomy. Most current reports on LALR-S8 are case series using one surgical approach, and there is a lack of multicenter data on identifying intersegmental planes using different approaches. In this study, the authors aimed to elucidate the short-term results of three different approaches for LALR-S8 for hepatocellular carcinoma (HCC), focusing on intersegmental plane determination, and to reflect on current practice regarding different approaches at multiple centers in China.
Materials and methods:
The clinical cohort data of 122 patients who underwent LALR-S8 for HCC at seven leading centers in China were retrospectively analyzed. The surgical procedures of all approaches were summarized and standardized according to the method of the Glissonean pedicle of segment 8 identification. The postoperative short-term outcomes and oncological results of the three approaches were evaluated and compared.
Results:
Three approaches were used: laparoscopic ultrasonography-guided indocyanine green fluorescent positive staining approach (11/122, 9.02%), hepatic vein-guided approach (99/122, 81.15%), and Glissonean indocyanine green fluorescent negative staining approach (12/122, 9.83%). Seven (5.73%) patients experienced complications according to the Clavien–Dindo classification, and the rate of grade ≥IIIa complications was 2.46%. The R0 resection rates among the groups (margin >1 mm) and the margin width showed no statistical difference.
Conclusion:
LALR-S8 is safe and feasible for treating HCC under standardized surgical techniques and appropriate surgical approaches. The three reported approaches had comparable short-term oncological outcomes, while the hepatic vein-guided approach was most commonly used.
Keywords: Glissonean approach, hepatic vein-guided approach, hepatocellular carcinoma, laparoscopic anatomical liver resection of segment 8
Introduction
Highlights
Anatomical resection improves outcomes of hepatocellular carcinoma.
We compared three approaches to identify and segment G8 in laparoscopic liver resection.
There were no significant differences in prognosis among the techniques.
A hepatic vein-guided approach is preferred by most surgeons.
Anatomical resection for hepatocellular carcinoma (HCC), defined as the removal of a functional area supplied by the portal territories of the Glissonean branches completely, has been shown to significantly reduce oncological recurrence and accelerate recovery compared with nonanatomical resection1. Although the advantages of minimal trauma and optimal rehabilitation have been well recognized and accepted as superiorities of laparoscopic liver resection against traditional open surgery, laparoscopic anatomical liver resection for segment 8 (LALR-S8) remains the most challenging laparoscopic procedure owing to its deep location in the upper abdominal cavity and close proximity to two major hepatic veins and the inferior vena cava. Direct access to the Glissonean pedicle of segment 8 (G8) is inconvenient owing to its high bifurcation from the right anterior pedicle and fickle anatomy variations2–4. According to the Iwate classification, laparoscopic S8 segmentectomy is rated 7–10 points (high difficulty)5. In the literature, S8 anatomical segmentectomy resection caused the largest blood loss and was the only procedure with a greater than 10% incidence of Clavien–Dindo (CD) grade>IIIa complications6. In most cases, G8 bifurcates into ventral and dorsal halves4. LALR-S8 is divided into three types (all, ventral region [S8v], or dorsal region [S8d]) according to the associated Glissonean branches7. The criteria for anatomical liver resection are correct dissection of the Glissonean pedicles and exposure of the signature hepatic veins as two landmarks8. Available reviews are mainly based on case reports or short case series, with no strong evidence to recommend one technique over the others9–11.
In the present study, the LALR-S8 approaches were classified into three types based on the methods used to identify and segment G8 and determine the hepatic intersegmental/sectional plane: the laparoscopic ultrasonography (LUS)-guided indocyanine green (ICG) fluorescent positive staining approach, the hepatic vein-guided approach, and the Glissonean ICG fluorescent negative staining approach (Fig. 1). These three approaches for determining the intersegmental plane of LALR-S8 for HCC were described and compared in detail, and the short-term results at multiple centers in China were reported.
Figure 1.
Diagram of the three different approaches. (A) LUS-guided ICG fluorescent positive staining approach. (B1) Hepatic vein-guided approach. The left dissection plane is defined according to the ischemic line after clamping the right anterior Glissonean pedicle. (B2) Hepatic vein-guided approach. The projection line of the MHV is marked under LUS guidance. (C) Glissonean ICG fluorescent negative staining approach. AFV, anterior fissure vein; G8, Glissonean pedicle of segment 8; G-ant, right anterior Glissonean pedicle; ICG, indocyanine green; IVC, inferior vena cava; LHV, left hepatic vein; LUS, laparoscopic ultrasonography; MHV, middle hepatic vein; P8, S8 portal vein; RHV, right hepatic vein.
Material and methods
A retrospective cohort analysis of the database of seven centers in China was performed between August 2019 and January 2023. Seven qualified hepatobiliary surgeons performed the operation. Each of these surgeons performs greater than 200 laparoscopic liver resections annually. Patients with pathologically confirmed HCC who underwent LALR-S8 were included (Fig. 2). Patients with HCC ultimately diagnosed by pathology, those who underwent LALR-S8, and those with complete exposure of the signature hepatic veins were also included. Patients with intrahepatic or extrahepatic metastasis; those who underwent open, robotic, hand-assisted, or hybrid techniques; those who underwent partial nonanatomical resections; and those who underwent treatment combined with segmentectomy or other operations were excluded. Ethical approvals were obtained from each respective institutional ethics committee and the research was retrospectively registered, which was conducted in accordance with the ethical guidelines outlined in the 1975 Declaration of Helsinki (6th revision, 2008). Informed consent from patients was deemed unnecessary by the ethics committee for this retrospective study. All patients underwent routine cardiopulmonary function, blood, and a biochemical examinations to exclude surgical and anesthetic contraindications. Each patient underwent abdominal computed tomography angiography, three-dimensional (3D) reconstruction, and enhanced MRI to confirm the portal territories pedicles feeding the tumor-bearing area, evaluate the distribution of the hepatic structure, and calculate the volume of the residual and standard liver. All patients were regularly followed up for chest and abdominal CT, alpha-fetoprotein tumor marker test, blood analysis, and biochemical examination every 3 months postoperatively. The primary endpoint of the study was to evaluate the postoperative short-term outcomes focusing on 90-day mortality after LALR-S8. Patients’ baseline characteristics, oncological results, and postoperative short-term outcomes and oncological results were compared among the three approaches. The work has been reported in line with the strengthening the reporting of cohort, cross-sectional, and case–control studies in surgery (STROCSS) criteria12.
Figure 2.
The study flowchart. HCC, hepatocellular carcinoma; ICG, indocyanine green; LALR-S8, laparoscopic anatomical liver resection of segment 8; LUS, laparoscopic ultrasonography.
Anesthesia and position
The supine position with a head-up tilt (30°) to the left and legs apart were adopted for patients after intravenous inhalation combined with anesthesia. A five-hole distribution of trocars was applied during liver resection. Pneumoperitoneum was established using a pressure of 11–13 mmHg and a central venous pressure of 3–5 cmH2O. To control bleeding from the inflow, most institutions performed the Pringle maneuver with intermittently cycles of 10–15 min clamping and 5 min release, whereas one institution used right Glissonean pedicle occlusion.
Surgical technique
LUS-guided ICG fluorescent positive staining approach (Fig. 3)
Figure 3.
LUS-guided ICG fluorescent positive staining approach. (A) Preoperative 3D reconstruction. (B) Schematic diagram of the self-developed locator. (C) The portal branches of tumor-bearing liver segments are punctured under LUS guidance. (D) S8 portal vein (P8) and puncture point are identified using LUS (arrow). (E) The parenchyma is transected along the MHV, and the V8v is exposed and divided. (F) Exposing and dividing the G8. (G) The intersegmental planes are determined along the fluorescent staining area. (H) The anatomical structure is clearly visible on the surgical field after anatomical S8 resection. 3D, three-dimensional; G8, Glissonean pedicle of segment 8; ICG, indocyanine green; LUS, laparoscopic ultrasonography; MHV, middle hepatic vein.
The LUS probe was inserted through a subxiphoid trocar and rotated axially on the liver surface to locate the P8 branch, and the puncture site on the body surface was empirically determined or assisted by a self-developed locator (Fig. 3B). The puncture position was finely adjusted according to the needle angle and probe direction. After P8 was punctured successfully using an 18–20-G percutaneous transhepatic bile duct drainage needle, ICG (1–3 ml, 0.025 mg/ml) was slowly injected to avoid retrograde ICG flow to the adjacent segments, and the portal territory of S8 was demarcated. After stable fluorescence imaging, LUS was used to determine whether the stained area was correct. The transection plane was directed using a fluorescence staining boundary, the middle hepatic vein (MHV) was fully exposed from cranial to caudal, and the remaining vein branches were safely ligated and cut. After ligation and transection of G8, the root of the right hepatic vein (RHV) was further separated under fluorescence guidance, and the RHV was fully exposed from cranial to caudal. Combined with LUS and ICG fluorescent navigation, the drainage vein of S8 (V8) was excised, and S8 was completely resected.
Hepatic vein-guided approach (Fig. 4)
Figure 4.
Hepatic vein-guided approach. (A) Preoperative 3D reconstruction. (B) The left dissection plane is defined according to the projection line of the MHV under ultrasound guidance. (C) The hepatic parenchyma is transected under the guidance of the MHV. (D) The S8 ventral Glissonean pedicle (G8v) is isolated and clamped. (E) The S8 dorsal Glissonean pedicle (G8d) is identified and isolated, then the intersegmental planes are determined along the ischemic area. (F) The RHV is exposed from cranial to caudal. (G) Exposing and dividing the V8d. (H) After the S8 resection, the MHV, V7, and RHV are fully exposed. 3D, three-dimensional; G8, Glissonean pedicle of segment 8; MHV, middle hepatic vein; RHV, right hepatic vein.
The origins of the MHV and RHV were exposed after dissection of the falciform and coronary ligaments. The left transection line was marked according to the projection of the MHV on the liver surface using LUS or the demarcation line between segments 8 and 4 after isolating and clamping the right anterior Glissonean pedicle (G-ant) from the hepatic hilum. A portion of the G8 roots was also marked using LUS. Parenchymal dissection was initiated at the root side of the MHV between the cutting line on the liver surface and the MHV and advanced from the cranial side. After parenchymal dissection being deeply initiated and full exposure, G8 was identified and cut at its root. The boundary of the ischemic area was clearly shown and the demarcation line was marked. Using the root of G8 and the inferior vena cava as landmark, S8 was hold to the ventral side, the liver parenchyma at the base of S8 was divided, and the root of the RHV was exposed toward the periphery.
Glissonean ICG fluorescent negative staining approach
The liver parenchyma was separated along Laennec’s capsule at the hilum via the Glissonean approach, exposing the G-ant. The proximal pedicle branches supplying the S5 segment were avoided or hanged for protection. Then, all the distal pedicles supplying the S8 segment were isolated and clamped extrahepatically at the hilum by climbing the branches step-by-step before parenchymal dissection. LUS was used to confirm the correct ischemic area, and the ischemic line was clearly marked on the liver surface using electrocautery. Then, ICG (5–10 ml, 0.025 mg/ml) was injected intravenously for negative staining, which can provide a clear demarcation line between S8 and adjacent segments. The rest of the procedure was the same as that of the hepatic vein-guided approach. The fluorescence guide was followed to cut off the vein branches into the tumor-bearing area, gradually reveal the major hepatic veins, and complete the resection of the target liver segment or subsegment. The same principle was applied to S8d resection (Fig. 5). After the dorsal branch of G8 was successfully isolated and clamped, the tumor-bearing areas were fully resected under fluorescence navigation.
Figure 5.
Glissonean ICG fluorescent negative staining approach. (A) Preoperative 3D-CT reconstruction showing S8 dorsal area (in blue) and S8 dorsal Glissonean pedicle (G8d1; G8d2). (B) The Glissonean approach is performed step-by-step from the liver hilum, aiming at the G8d1. (C) Isolating and clamping the G8d2. (D) The liver parenchyma is transected along the ICG fluorescence guide. (E) Cutting the G8d2. (F) Cutting the G8d1. (G) The root of the RHV is exposed. (H) Surgical field after anatomical S8 dorsal area resection. (G5d, S5 dorsal Glissonean pedicle) 3D, three-dimensional; CT, computed tomography; G8, Glissonean pedicle of segment 8; RHV, right hepatic vein.
Statistical analysis
The R language software (version 4.2.2; R Foundation for Statistical Computing) was used to process and analyze the data. All data were tested using standard normality tests (Shapiro–Wilk test) before statistical analysis. The continuous quantitative data were presented as means±SD if they were normally distributed; one-way analysis of variance was used for multigroup comparison; a nonparametric test was applied when performing statistical analysis and median M[P25, P75] values were used to describe the data if they were not normally distributed; and a multigroup independent sample rank sum test (Kruskal–Wallis H) was used for comparisons between multiple groups. The number of cases (%) was used to describe the data when counting them. The χ 2 test was used for intergroup comparison. Fisher’s exact probability method was used when the χ 2 test conditions were unmet. All tests were two-sided, and statistical significance was set at P <0.05.
Results
The baseline characteristics of the three groups are summarized in Table 1, and there were no statistically significant differences. Among the 122 patients who underwent LALR-S8 for HCC, 109 underwent S8 resection, six underwent S8v resection, and seven underwent S8d resection (Table 2). The LUS-guided ICG fluorescent positive staining approach, the hepatic vein-guided approach, and the Glissonean ICG fluorescent negative staining approach were used in 11 (9.02%), 99 (81.15%), and 12 (9.83%) patients, respectively. Furthermore, 103 patients had hepatitis [101 with hepatitis B (82.79%) and two with hepatitis C (1.64%)], and 72 (59.02%) had liver cirrhosis. Of all patients, 117 (95.90%) were Child–Pugh grade A, and the preoperative ICG retention rate was 4.30% (2.70, 6.60). Moreover, 115 patients had one lesion (94.26%) and seven had two lesions (5.74%), with a size of 34.5 (24.00, 41.00) mm. During the 3D reconstruction, a median resection volume of 235.50 (180.00, 306.00) ml was planned, accounting for 20% (14.60, 25.50) of the total liver volume. The median intraoperative blood loss was 200 (100, 300) ml, and the operative time was 229.54±78.98 min in all patients. Seven patients had undergone previous abdominal surgery, whereas three had undergone conversion therapy.
Table 1.
Patients’ baseline characteristics.
| LUS-guided ICG fluorescent positive staining approach | Hepatic vein-guided approach | Glissonean ICG fluorescent negative staining approach | |||
|---|---|---|---|---|---|
| Total (n=122) | n=11 (9.02%) | n=99 (81.15%) | n=12 (9.83%) | P | |
| Age | 56.00 (48.00;66.00) | 56.00 (54.00;66.00) | 56.00 (47.00;66.00) | 57.00 (52.50;63.50) | 0.724 |
| Sex | 0.597 | ||||
| Female | 17 (13.93%) | 1 (9.09%) | 13 (13.13%) | 3 (25.00%) | |
| Male | 105 (86.07%) | 10 (90.91%) | 86 (86.87%) | 9 (75.00%) | |
| BMI (kg/m2) | 23.51±2.88 | 23.59±2.81 | 23.52±2.94 | 23.40±2.60 | 0.987 |
| Hepatitis B/C virus | 0.364 | ||||
| B | 101 (82.79%) | 9 (81.82%) | 84 (84.85%) | 8 (66.67%) | |
| C | 2 (1.64%) | 0 (0.00%) | 2 (2.02%) | 0 (0.00%) | |
| Neither | 19 (15.57%) | 2 (18.18%) | 13 (13.13%) | 2 (33.33%) | |
| Cirrhosis | 0.083 | ||||
| No | 50 (40.98%) | 8 (72.73%) | 37 (37.37%) | 5 (41.67%) | |
| Yes | 72 (59.02%) | 3 (27.27%) | 62 (62.63%) | 7 (58.33%) | |
| Comorbidities | 0.445 | ||||
| No | 82 (67.21%) | 8 (72.73%) | 64 (64.65%) | 10 (83.33%) | |
| Yes | 40 (32.79%) | 3 (27.27%) | 35 (35.35%) | 2 (16.67%) | |
| BCLC | 0.106 | ||||
| 0 | 18 (14.75%) | 1 (9.09%) | 17 (17.17%) | 0 (0.00%) | |
| A | 103 (84.43%) | 10 (90.91%) | 82 (82.83%) | 11 (91.67%) | |
| B | 1 (0.82%) | 0 (0.00%) | 0 (0.00%) | 1 (8.33%) | |
| CNLC | 0.014 | ||||
| Ia | 98 (80.33%) | 7 (63.64%) | 84 (84.85%) | 7 (58.33%) | |
| Ib | 23 (18.85%) | 4 (36.36%) | 15 (15.15%) | 4 (33.33%) | |
| IIa | 1 (0.82%) | 0 (0.00%) | 0 (0.00%) | 1 (8.33%) | |
| ECOG: 0 | 122 (100.00%) | 11 (100.00%) | 99 (100.00%) | 12 (100.00%) | |
| Child–Pugh grade | >0.999 | ||||
| A | 117 (95.90%) | 11 (100.00%) | 94 (94.95%) | 12 (100.00%) | |
| B | 5 (4.10%) | 0 (0.00%) | 5 (5.05%) | 0 (0.00%) | |
| Preoperative ICG retention rate (%) | 4.30 (2.70; 6.60) | 2.60 (2.50,4.05) | 4.30 (2.70; 6.60) | 5.20 (3.50; 7.80) | 0.309 |
| Previous surgery | 0.182 | ||||
| No | 115 (94.26%) | 9 (81.82%) | 94 (94.95%) | 12 (100.00%) | |
| Yes | 7 (5.74%) | 2 (18.18%) | 5 (5.05%) | 0 (0.00%) | |
| Conversion therapy | 0.469 | ||||
| No | 119 (97.54%) | 11 (100.00%) | 97 (97.98%) | 11 (100.00%) | |
| Yes | 3 (2.46%) | 0 (0.00%) | 2 (2.02%) | 1 (0.00%) |
BCLC, Barcelona clinic liver cancer; CNLC, China liver cancer staging; ECOG, Eastern Cooperative Oncology Group; ICG, indocyanine green.
Table 2.
Intraoperative data.
| LUS-guided ICG fluorescent positive staining approach | Hepatic vein-guided approach | Glissonean ICG fluorescent negative staining approach | |||
|---|---|---|---|---|---|
| Total (n=122) | n=11 (9.02%) | n=99 (81.15%) | n=12 (9.83%) | P | |
| Lesion size (mm) | 34.50 (24.00;41.00) | 30.00 (18.00;45.00) | 35.00 (24.00;41.00) | 30.00 (25.00;50.50) | 0.838 |
| Number of lesions | 0.082 | ||||
| 1 | 115 (94.26%) | 9 (81.82%) | 95 (95.96%) | 11 (91.67%) | |
| 2 | 7 (5.74%) | 2 (18.18%) | 4 (4.04%) | 1 (8.33%) | |
| Distance from major vessels <1 cm | 0.029 | ||||
| No | 93 (76.23%) | 7 (63.64%) | 80 (80.81%) | 6 (50.00%) | |
| Yes | 29 (23.77%) | 4 (36.36%) | 19 (19.19%) | 6 (50.00%) | |
| Distance from liver capsule >1 cm | 0.020 | ||||
| No | 59 (48.36%) | 9 (81.82%) | 42 (41.42%) | 8 (66.67%) | |
| Yes | 63 (51.64%) | 2 (18.18%) | 57 (57.78%) | 4 (33.33%) | |
| Preoperative resection volume (ml) | 235.50 (180.00;306.00) | 243.00 (165.00;330.00) | 238.00 (186.00;305.00) | 175.50 (116.00;339.50) | 0.401 |
| PRLV/TLV % | 20.00 (14.60;25.50) | 22.00 (15.00;25.00) | 20.00 (14.80;25.60) | 15.93 (9.84;25.53) | 0.513 |
| R0 resection: Y | 122 (100.00%) | 11 (100.00%) | 99 (100.00%) | 12 (100.00%) | |
| Minimum surgical margin width (mm) | 11.50 (10.00;20.00) | 10.00 (8.00;20.00) | 15.00 (10.00;20.00) | 5.00 (2.00;15.00) | 0.076 |
| Total Pringle maneuver time (min) | 45.00 (20.00;68.00) | 63.00 (60.00;79.00) | 40.00 (10.00;66.00) | 60.00 (46.00;77.50) | 0.001 |
| Inflow occlusion | 0.005 | ||||
| Total Pringle maneuver | 118 (96.72%) | 11 (100%) | 98 (98.99%) | 9 (75.00%) | |
| Right Glissonean pedicle occlusion | 4 (3.28%) | 0 (0.00%) | 1 (1.01%) | 3 (25.00%) | |
| Number of Pringle maneuvers | 3.00 (2.00;4.00) | 4.00 (3.00;4.00) | 3.00 (1.00;4.00) | 3.50 (2.25;4.00) | 0.074 |
| Type of resection | 0.030 | ||||
| S8 | 109 (89.34%) | 8 (72.73%) | 92 (92.93%) | 9 (75.00%) | |
| S8d | 7 (5.74%) | 2 (18.18%) | 3 (3.03%) | 2 (16.67%) | |
| S8v | 6 (4.92%) | 1 (9.09%) | 4 (4.04%) | 1 (8.33%) | |
| ICG staining method | <0.001 | ||||
| None | 93 (76.23%) | 0 (0.00%) | 86 (86.87%) | 7 (58.33%) | |
| Positive staining | 13 (10.66%) | 11 (100%) | 2 (2.02%) | 0 (0.00%) | |
| Negative staining | 16 (13.11%) | 0 (0.00%) | 11 (11.11%) | 5 (41.67%) | |
| Numbers of G8 | 0.082 | ||||
| ≤2 | 106 (86.89%) | 9 (81.82%) | 87 (87.88%) | 10 (83.33%) | |
| >2 | 16 (13.11%) | 2 (18.18%) | 12 (12.12%) | 2 (16.67%) | |
| Operative time (min) | 229.54±78.98 | 261.18±75.56 | 229.47±81.91 | 201.08±41.92 | 0.191 |
| Intraoperative blood loss (ml) | 200.00 (100.00;300.00) | 100.00 (100.00;200.00) | 200.00 (100.00;300.00) | 75.00 (50.00;175.00) | 0.025 |
| Blood transfusion | >0.999 | ||||
| No | 117 (95.90%) | 11 (100.00%) | 94 (94.95%) | 12 (100.00%) | |
| Yes | 5 (4.10%) | 0 (0.00%) | 5 (5.05%) | 0 (0.00%) |
ICG, indocyanine green; PRLV/TLV, preoperative resection volume/total liver volume; S8, segment 8; S8d, S8 dorsal region; S8v, S8 ventral region.
All patients had negative resection margins, and the minimum surgical margin width was 11.5 (10.00, 20.00) mm. The median length of postoperative hospital stay was 8.0 (6.00, 9.00) days. Seven (5.73%) patients experienced complications according to the CD classification; the rate of grade ≥IIIa complications was 2.46% (Table 3). One patient experienced an improvement in liver failure after drug treatment. One patient experienced a bile leak, which was resolved spontaneously. Three patients developed ascites (one CD II requiring drainage and two CD I that spontaneously resolved), all of which occurred after S8 resection. Two patients had a postoperative infection requiring CT-guided puncture drainage. No postoperative bleeding or mortality was observed. One patient was readmitted to the hospital for tumor recurrence.
Table 3.
Postoperative short-term outcomes.
| LUS-guided ICG fluorescent positive staining approach | Hepatic vein-guided approach | Glissonean ICG fluorescent negative staining approach | |||
|---|---|---|---|---|---|
| Total (n=122) | n=11 (9.02%) | n=99 (81.15%) | n=12 (9.83%) | P | |
| 90 days mortality | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | – |
| Postoperative hospital stay (days) | 8.00 [6.00;9.00] | 7.00 [6.00;9.00] | 8.00 [6.00;9.00] | 5.50 [5.00;7.50] | 0.052 |
| Readmission | >0.999 | ||||
| No | 119 (97.54%) | 11 (100.00%) | 96 (96.97%) | 12 (100.00%) | |
| Yes | 3 (2.46%) | 0 (0.00%) | 3 (3.03%) | 0 (0.00%) | |
| Recurrence | 0.090 | ||||
| No | 121 (99.18%) | 10 (90.91%) | 99 (100.00%) | 12 (100.00%) | |
| Yes | 1 (0.82%) | 1 (9.09%) | 0 (0.00%) | 0 (0.00%) | |
| Follow-up (months) | 12.00 [6.00;19.00] | 8.00 [1.00;16.00] | 13.00 [7.00;20.00] | 5.00 [2.00;10.00] | 0.039 |
| Clavien–Dindo complication grade | >0.999 | ||||
| <IIIa | 119 (97.54%) | 11 (100.00%) | 96 (96.97%) | 12 (100.00%) | |
| ≥IIIa | 3 (2.46%) | 0 (0.00%) | 3 (3.03%) | 0 (0.00%) | |
| Liver failure | >0.999 | ||||
| No | 121 (99.18%) | 11 (100.00%) | 98 (98.99%) | 12 (100.00%) | |
| Yes | 1 (0.82%) | 0 (0.00%) | 1 (1.01%) | 0 (0.00%) | |
| Ascites | >0.999 | ||||
| No | 119 (97.54%) | 11 (100.00%) | 96 (96.97%) | 12 (100.00%) | |
| Yes | 3 (2.46%) | 0 (0.00%) | 3 (3.03%) | 0 (0.005) | |
| Bile leakage | >0.999 | ||||
| No | 121 (99.18%) | 11 (100.00%) | 98 (98.99%) | 12 (100.00%) | |
| Yes | 1 (0.82%) | 0 (0.00%) | 1 (1.01%) | 0 (0.00%) | |
| Infection | >0.999 | ||||
| No | 120 (98.36%) | 11 (100.00%) | 97 (97.98%) | 12 (100.00%) | |
| Yes | 2 (1.64%) | 0 (0.00%) | 2 (2.02%) | 0 (0.00%) | |
| Bleeding: N | 122 (100.00%) | 11 (100.00%) | 99 (100.00%) | 12 (100.00%) |
ICG, indocyanine green; PRLV/TLV, preoperative resection volume/total liver volume.
Patients who underwent the LUS-guided ICG fluorescent positive staining approach required more operative time and were enrolled in only two centers. The majority (81.15%) chose the hepatic vein-guided approach. Patients who underwent the Glissonean ICG fluorescent negative staining approach had significantly less blood loss and preoperative resection volume (P=0.023). The R0 resection rates between the groups (margin >1 mm) and the margin width were not significantly different (Table 2). Notably, there was no significant correlation between the center volume and morbidity or mortality and no significant difference in complication and recurrence rates existed among the three groups (Table 3).
Discussion
In this study, we examined the short-term results of three different approaches for LALR-S8 HCC cases. According to the Tokyo Expert Consensus Meeting held in February 2021, anatomical segmentectomy is defined as the removal of the liver area confined within the responsible portal territory (or territories) of the third-order portal venous branches completely13. This unity of concepts solved the problem of the Brisbane 2000 Terminology for Liver Anatomy and Resections, which, based on Couinaud’s segments, did not address the identification of segmental and subsegmental anatomic territories borders14. The hepatic intersegmental or sectional plane was defined by the boundary that watershed each portal venous territory15,16. Hepatic veins coursing the intersegmental planes are defined as intersegmental, respectively, and act as a representative landmarks during the liver parenchyma transection appropriately by continuous exposure in the cutting plane17.
The goal of LALR-S8 is to correctly find the target liver pedicle supplying S8 and determine the intersegmental plane. Makuuchi et al.18 pioneered the method of ultrasound-guided puncture of the target portal vein, which nourishes tumor segments, and, then, injecting dye into it. In 2008, Aoki et al.19 first reported the application of fluorescence imaging for segmental localization during liver surgery. Ishizawa et al.20 applied the Aoki technology in laparoscopic hepatectomy and reported positive and negative staining techniques in 2012. Currently, the LUS-guided ICG fluorescent positive staining approach has become a standard technique for improving the accuracy of laparoscopic anatomical hepatectomy because it not only compensates for the defect that the ischemic line is only shown on the surface of the liver, but also shows a clear fluorescent demarcation line in the intersegmental plane in real time, especially in patients with unclear anatomy due to inflammatory adhesions, cirrhosis, and/or multiple liver surgeries21. This approach requires professional knowledge of liver ultrasound imaging, skilled LUS use, and puncture techniques, which require a learning curve22. Our previous study showed a success rate of staining of 10%, and the failure may be attributed to the fact that ICG is countercurrent to the adjacent hepatic pedicle or punctured into the wrong branch or hepatic vein tributary during the injection23. We suggest that the puncture point of the target portal vein branch should be as far from the adjacent branches as possible, and the injection process should be slow to avoid reflux. With the help of our self-developed surgical positioning puncture device, the puncture success rate can be improved. We recommend that the puncture concentration be 0.025 mg/ml, and 1–3 ml should be injected first. After the fluorescence is stable and no longer strengthened, a dose of 1 ml should be continued each time if the development is poor. When the number of target portal vein branches to be punctured is large (≥3) or the diameter is less than 3 mm, the difficulty of puncture significantly increases; other approaches should be adopted, or the portal vein branch that can distinguish the intersegmental plane between S8 and S5 should be preferentially selected for puncture.
The Glissonean ICG fluorescent negative staining approach does not require the surgeon to master the LUS and puncture techniques and can identify each targeted segmental or subsegmental pedicle via the Glissonean approach according to iconic landmarks and gates, including Laennec’s capsule23,24. Berardi et al.25 reported favorable short-term results using this approach in 86 cases of parenchyma-preserving laparoscopic anatomic hepatectomy. With ICG-negative staining, the borders of the resection should be identified clearly, and all the liver tissue fed by the specific pedicle should eventually be removed. In the present study, the preoperative resection volume and blood loss were significantly less in 12 patients who underwent the Glissonean ICG fluorescent negative staining approach than in those who underwent the other two approaches. This may indicate that the Glissonean ICG fluorescent negative staining approach can achieve anatomical hepatectomy by maximizing the preservation of functional remnant liver tissue and reducing intraoperative bleeding. However, not every LALR-S8 can be treated using this approach because when the targeted Glissonean pedicle is peripheral and deep, the identification and clamp phases may be time-consuming and challenging, nontarget Glissonean pedicles may be encountered and have to be sacrificed, and a more peripheral Glissonean dissection may increase the risk of postoperative biliary leakage and delayed biliary stricture26. In deeper G8 dorsal or ventral branches requiring exploration, the Glissonean approach does not show a significant advantage, destroying the hepatic hilum and possibly making the next hepatectomy more difficult7,27. This approach requires careful preoperative planning during preoperative simulation to ensure that the correct pedicle feeding S8 has been removed and to reduce the incidence of unnecessary injury and bile leakage.
The results of a survey of global experts showed that only 17.6% chose the isolation of the root of G8 from the hepatic hilum, whereas 64.7% chose parenchymal dissection from the liver surface to find and isolate the root of G81, which was classified as the hepatic vein-guided approach in the present study. This is consistent with our results that 81.15% of the cases were selected using the hepatic vein-guided approach. After parenchymal dissection, the MHV and RHV can be exposed safely and quickly from the root because their roots have fewer branches and shallow in position28. Exposure of the hepatic vein from cranial to caudal positions can lead to early blockade of branches and reduce bleeding caused by hepatic vein injury29. The left transection plan can be determined by the cutting line and MHV using LUS or defined by temporary clamping of the right anterior hepatic pedicle2. When LUS demarcates the projection of the MHV, the cutting line should be moved 0.5 cm to the left side to tilt the disconnection plane slightly clockwise, which can ensure that the MHV is on the left plane. The limitation of this approach is that it is difficult to clearly determine the location of G8 and confirm the plane between segments 5 and 8. Ome et al.7 reported that G8 roots were easily identified by dividing the parenchyma deeply to the length of 1–2 cm on the right side of the confluence of a hepatic vein branch that joined the MHV and ran between segments 5 and 8. It may not be a true anatomical resection; however, we still believe that it is oncologically acceptable because the short-term results also show no statistical difference between the three methods in terms of short-term oncological prognosis, which suggests that any of the three methods can benefit patients. However, this needs to be further elucidated using higher-level evidence.
Of note, preliminary results showed no significant statistical difference in the advantages of oncology and postoperative recovery between following the hepatic vein and following the ICG fluorescent boundary when determining the intrahepatic plane. The frequency of signature hepatic veins on the fluorescent-guided intrahepatic plane was 100%, which indicates that there is no contradiction between them and may provide an important reference for defining true anatomical resection and determining standardized methods for anatomical resection. However, well-designed studies are needed to compare postoperative changes in relevant indicators.
The significance of this study is that it is entirely based on real-world experience at multiple centers in China, avoiding the subjectivity and bias of data from a single center. This study is not only the first comparative analysis of patient and surgical data associated with different approaches but also puts forward our suggestions based on the applicability and limitations of each approach. This provides a reference for standardizing surgical procedures and designing more precise experiments for S8 segment resections.
In this study, the enrolled centers were all leading institutions for laparoscopic liver resection in China, all surgeons were major experts in the field of laparoscopic hepatectomy, and the learning curve had already plateaued. However, this study also had some limitations. First, there was a technical imbalance between each center, and surgeons had their preferences on the choice of surgical approaches, which might have led to data bias. Second, this study was retrospective, and patients were selected. More prospective studies with precise designs are needed to further compare the advantages and disadvantages of the three approaches in oncology. We will revise our recommendations as soon as more reliable data become available.
Conclusion
In conclusion, with standardized indications and techniques, the three approaches for LALR-S8 are safe and feasible in specialized centers, with good short-term postoperative outcomes and oncological efficacy. Compared with the other two approaches, the hepatic vein-guided approach was preferred by most surgeons. The ICG fluorescent portal territory positive/negative staining approach may be a novel choice, but more evidence is needed.
Ethical approval
Approval by Ethics Committee of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Approval No. 21/017-2688.
Consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Sources of funding
Scientific Research Fund of Education Department of Yunnan Province (No. 2023J767).
Author contribution
H.W. and J.L.: conceptualization; Q.Z., Y.W., X.L., W.C., F.T., X.W., H.X., J.C., N.Z., Z.Y., and C.T.: investigation; X.W., H.W., and J.L.: data curation and methodology; X.W., J.C., and J.L.: writing – original draft; H.W., J.L., and X.W.: writing – review and editing.
Conflicts of interest disclosure
All authors have declared no conflicts of interest.
Research registration unique identifying number (UIN)
Name of the registry: Protocol Registration and Results System (PRS).
Unique identifying number or registration ID: NCT02009176.
Hyperlink to your specific registration (must be publicly accessible and will be checked): https://register.clinicaltrials.gov/
Guarantor
Xingru Wang.
Data availability statement
Available upon reasonable request.
Provenance and peer review
Not commissioned, externally peer-reviewed.
Acknowledgements
Assistance with the study: none.
Footnotes
Xingru Wang, Jianwei Li, and Jun Cao contributed equally to this work.
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Published online 11 September 2023
Contributor Information
Xingru Wang, Email: hongxing0060@163.com.
Jianwei Li, Email: 594457357@qq.com.
Jun Cao, Email: 727106893@qq.com.
Qifan Zhang, Email: qifanzhangsmu@126.com.
Yonggang Wei, Email: yourwyg@163.com.
Wei Cheng, Email: chengwei@hunnu.edu.cn.
Xiao Liang, Email: srrshlx@zju.edu.cn.
Feng Tian, Email: tianfeng@tmmu.edu.cn.
Xin Wang, Email: 568327379@qq.com.
Hongwei Xu, Email: hongweixu26@hotmail.com.
Jie Chen, Email: enkeyc@163.com.
Ning Zhou, Email: zhouning565@hunnu.edu.cn.
Zaibo Yang, Email: 3160105319@zju.edu.cn.
Changcheng Tao, Email: dr.taocc@foxmail.com.
Hongguang Wang, Email: wanghongguang301@163.com.
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Associated Data
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Data Availability Statement
Available upon reasonable request.