Efficiency and safety of laparoscopic left hemihepatectomy: A study of intrathecal vs extrathecal Glissonean pedicle techniques

Abstract

BACKGROUND

Selective hemihepatic vascular occlusion is utilized in both right and left hemihepatectomies to preserve blood supply to the intact lobe, maintain hemodynamic stability, and mitigate surgical risks. While this technique encompasses both intrathecal and extrathecal Glissonean pedicle transection methods, there is a lack of systematic comparative reports on these two approaches.

AIM

To retrospectively analyze the clinical data of patients with hepatocellular carcinoma (HCC) undergoing laparoscopic anatomical hepatectomy in our hospital to explore the feasibility, safety, and short- and long-term efficacy of extrathecal and intrathecal Glissonean pedicle transection methods in laparoscopic left hemihepatectomy.

METHODS

A retrospective study was performed to analyze the clinical data of 49 HCC patients who underwent laparoscopic left hemihepatectomy from January 2019 to December 2022 in our hospital. These patients were divided into extrathecal Glissonean pedicle transection (EGP) group (n = 24) and intrathecal Glissonean pedicle transection (IGP) group (n = 25) according to the different approaches used for selective hemihepatic vascular occlusion. The perioperative indicators, liver function indexes, complications, and follow-up findings were compared between these two groups.

RESULTS

The surgeries were smooth in both groups, and no perioperative death was noted. The hepatic pedicle transection time and the operation time were (16.1 ± 2.3) minutes and (129.6 ± 19.0) minutes, respectively, in the EGP group, which were significantly shorter than those in the IGP group [(25.5 ± 2.4) minutes and (184.8 ± 26.0) minutes, respectively], both P < 0.01. There were no significant differences in intraoperative blood loss, time to anal exhaust, hospital stay, drain indwelling time, and postoperative liver function between the two groups (all P > 0.05). The incidence of postoperative complications showed no significant difference [16.67% (4/24) vs 16.0% (4/25), P > 0.05). All the 49 HCC patients were followed up after surgery (range: 11.2-53.3 months; median: 36.4 months). The overall survival rate and disease-free survival rate were not significantly different (both P > 0.05).

CONCLUSION

Both extrathecal and intrathecal Glissonean pedicle approaches are effective and safe hepatic inflow occlusion techniques in laparoscopic left hemihepatectomy for HCC. However, the extrathecal approach simplifies the hepatic pedicle transection, shortens the operation time, and increases the surgical efficiency, making it a more feasible technique.

Key Words: Hepatocellular carcinoma; Laparoscopy; Extra-Glissonian approach; Intra-Glissonian approach; Surgical efficiency; Surgical safety

Core Tip: Selective hemihepatic vascular occlusion is currently applied in both right and left hemihepatectomies to preserve blood supply to the intact lobe, ensure hemodynamic stability, and mitigate surgical risks. However, few studies have compared the extra-Glissonian approach and intra-Glissonian approach in this procedure. The present study explored the feasibility, safety, and short- and long-term efficacy of extrathecal and intrathecal Glisson pedicle approaches in laparoscopic left hemihepatectomy.

INTRODUCTION

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, with surgical resection being the mainstay of treatment. The recent years have witnessed the rapid advances in laparoscopic liver surgery. Evidence suggests that laparoscopic hepatectomy has similar effectiveness to that of traditional open liver resection, with notable advantages in surgical trauma and postoperative recovery[1]. However, due to the complex anatomy of the liver and the abundant blood supply, laparoscopic left hepatectomy is highly challenging and risky, necessitating the exploration of different hepatic inflow blocking techniques under laparoscopy[2].

Hepatic inflow occlusion plays an important role in the prevention of intraoperative hemorrhage and postoperative liver failure[3]. Total hepatic inflow occlusion technique is primarily utilized in liver resection procedures as it substantially diminishes the risk of significant bleeding; nevertheless, it may also lead to considerable hemodynamic instability[4]. In recent years, selective hemihepatic vascular occlusion is utilized in both right and left hemihepatectomies to preserve blood supply to the intact lobe, maintain hemodynamic stability, and mitigate surgical risks[5]. While this technique encompasses both intrahepatic and extrathecal Glissonean pedicle transection (EGP) methods, there is a lack of systematic comparative reports on laparoscopic intrathecal and extrathecal dissection techniques. This study retrospectively analyzed the clinical data of patients undergoing laparoscopic anatomical hepatectomy in our center to explore the feasibility, safety, and short- and long-term efficacy of extrathecal and intrathecal Glissonean pedicle transection (IGP) methods in laparoscopic left hemihepatectomy.

MATERIALS AND METHODS

General data

The clinical data of 49 patients (33 males and 16 females) with left HCC admitted to the Department of Hepatobiliary and Pancreatic Surgery of Puer People’s Hospital from January 2019 to December 2022 were retrospectively analyzed. The inclusion criteria were as follows: (1) Diagnosed with HCC by preoperative examinations and postoperative pathology and undergoing laparoscopic surgery; (2) With an American Society of Anesthesiologists Standard grade of ≤ II; (3) The tumor was isolated to the left hemiliver, and the procedure for resecting the left hemiliver was conducted using a laparoscopic approach; (4) The Child-Pugh liver function classification was at least class B, with ICG-R15 below 10%; and (5) Signed the informed consent forms, and the study was approved by the Hospital Ethics Committee. The exclusion criteria were: (1) With severe underlying diseases and/or psychological or psychiatric disorders; (2) Conversion to laparotomy; (3) The tumor presented as multiple lesions or when the opportunity for surgical intervention had been missed; or (4) With a history of upper abdominal surgery and/or those who could not tolerate pneumoperitoneum. The patients were divided into extrathecal Glissonean pedicle transection (EGP) group (n = 24) and intrathecal Glissonean pedicle transection (IGP) group (n = 25) according to the different approaches used for selective hemihepatic vascular occlusion. The baseline data were matched between these two groups (all P > 0.05; Table 1). The study had been approved by the Ethics Committee of Puer People's Hospital (approval No. 2024-001-01).

Table 1 Comparisons of general data and tumor status between the two groups.

	EGP group	IGP group	Statistics	P value
Age (years)	54.9 ± 11.4	54.6 ± 12.9	t = 0.103	0.919
Sex (male/female)	16/8	17/8	χ2 = 0.01	0.921
BMI (kg/m2)	23.5 ± 1.8	24.4 ± 2.2	t = 1.642	0.107
ASA grade (I-II)	17/7	21/4	χ2 = 1.219	0.26
Child-Pugh class (A/B)	16/8	16/9	χ2 = 0.038	0.845
Tumor diameters (cm)	4.46 ± 0.83	4.20 ± 0.68	t = 1.150	0.256
HBsAg (negative/positive)	8/16	5/20	χ2 = 1.117	0.291

EGP: Extrathecal Glissonean pedicle transection; IGP: Intrathecal Glissonean pedicle transection; BMI: Body mass index; ASA: American Society of Anesthesiologists; HBsAg: Hepatitis B surface antigen.

Surgical methods

In the EGP group, the patient was placed in a herringbone position, with a small (1 cm) longitudinal incision created at the lower edge of the umbilicus. The pneumoperitoneum was created, with the air pressure being maintained at 13 mmHg (1 mmHg = 0.133 kPa). The laparoscope was inserted via the subumbilical trocar. Two 12 mm trocars were inserted through an incision at the costal margin of left midclavicular line and an incision at the costal margin of right midclavicular line as the main operating ports, two 5 mm trocar was placed at the left and right anterior axillary lines as the auxiliary operating ports, and a laparoscope was placed in an observation port for routine exploration of the abdominal cavity. The left lobe of the liver was dissociated firstly, and the ligaments around the liver were severed. The portal plate was opened, and a small amount of liver tissues were removed when the dissection was difficult. After the left Glisson pedicle was dissected, anterior-to-posterior separation was performed at the left Glisson’s sheath gap and liver parenchyma and then continued between the Glisson’s sheath and the left caudal lobe of liver parenchyma. The left Glisson’s pedicle was bypassed and suspended with an 18F urethral catheter (Figure 1A). The surrounding ligaments were severed using an ultrasound knife to dissociate the left liver and expose the second hepatic hilum. Liver resection line was marked on the left side of the ischemic line on the surface of left liver using an electric hook. The hepatic parenchyma was divided with a high-intensity focused ultrasound (HIFU). Endo-GIA closure and dissection were performed upon the estimated reaching of the left hepatic vein. After the incision was enlarged, the pathological tissue was harvested en bloc and placed in a specimen bag. Postoperatively, potential hepatic bleeding and bile leakage at the cutting surface were examined. Prolene sutures were applied if necessary, and adequate hemostasis was performed at the cutting surface. Two abdominal drains were routinely placed.

Figure 1 Different hilar occlusion approaches. A: Extrathecal occlusion of the left hepatic hilum; B: Intrathecal occlusion of the left hepatic hilum.

Preliminary steps (such as body position and trocar layout) and preparation in the IGP group were the same as those in the EGP group. The transection of the liver pedicles was as follows: The first hilum of the liver was dissected and exposed. Then, the tissues inside the Glisson’s sheath were carefully separated to fully expose the left branch of the portal vein, the left hepatic artery, and the left hepatobiliary duct. Then, the Hem-o-lok was applied to clamp or sever intrathecal ducts one after another (Figure 1B). Clear ischemia lines might appear on the liver surface. The other steps were the same as in EGP group.

Main measures

(1) Perioperative indicators: The hepatic pedicle transection time, operation time, intraoperative blood loss, time to anal exhaust, hospital stay, and drain indwelling time were compared between two groups; (2) Liver function markers: Fasting peripheral venous blood was collected on days 1, 3, and 5 after operation, and the levels of total bilirubin (TBIL), aspartate aminotransferase (AST), and alkaline phosphatase were measured using an automatic biochemical analyzer; (3) Complications: The occurrence of complications such as postoperative hemorrhage, bile leakage, and pleural effusion was compared between these two groups; and (4) Follow-up: Overall survival (OS) and disease-free survival (DFS) rates were calculated for patients with pathologically confirmed HCC. Alpha-fetoprotein testing, abdominal color ultrasound, chest and abdominal computed tomography (CT), and other examinations were performed regularly at inpatient and outpatient settings, and the survivals and tumor recurrence were inquired by follow-up visits and telephone calls. Follow-up was conducted once every 3 months as of January 31, 2024 or till loss to follow-up/death.

Statistical analysis

The statistical analysis was performed using the SPSS 19.0 software. Normally distributed measurement data were compared using two independent samples t-test, and the non-normally distributed measurement data were presented using the medians (P25, P75) and compared using the Mann-Whitney U test. Numeration data were compared using χ² test. Survivals were analyzed using the Kaplan–Meier curves and log rank test. A P value of < 0.05 was considered statistically significant.

RESULTS

Comparison of perioperative indicators

The EGP group had significantly shorter hepatic pedicle dissection time and operation time than the IGP group (both P < 0.000). However, there were no significant differences in intraoperative blood loss, time to anal exhaust, hospital stay, drain indwelling time, and postoperative liver function between these two groups (all P > 0.05; Table 2).

Table 2 Comparison of perioperative indicators between the two groups.

	EGP group	IGP group	Statistics	P value
Operation time (minute)	129.6 ± 19.0	184.8 ± 26.0	t = 8.444	0.000
Hepatic pedicle transection time (minute)	16.1 ± 2.3	25.5 ± 2.4	t = 14.016	0.000
Intraoperative blood loss (mL)	347.1 ± 118.3	306.0 ± 110.2	t = 1.259	0.214
Time to anal exhaust (hour)	33.7 ± 10.7	31.0 ± 8.6	t = 0.945	0.349
Drain indwelling time (day)	2.25 (2.3)	3.0 (2.3)	Z = 0.991	0.322
Hospital stay (day)	7 (6.8)	7 (6.7)	Z = 1.730	0.084

EGP: Extrathecal Glissonean pedicle transection; IGP: Intrathecal Glissonean pedicle transection.

Comparison of liver function indexes

There were no significant differences in TBIL, AST and alanine aminotransferase between the two groups on days 1, 3, and 5 after surgery (all P > 0.05; Table 3).

Table 3 Comparison of postoperative liver function indexes between the two groups.

	Groups	Post-op day 1	Post-op day 3	Post-op day 5
TBIL (μmoL/L)	EGP group	57.80 ± 1.72	48.46 ± 5.45	32.46 ± 1.56
	IGP group	57.02 ± 2.56	47.6 ± 3.04	32.82 ± 1.51
	Statistics	t = 1.253	t = 0.707	t = 0.814
	P value	0.216	0.483	0.420
AST (U/L)	EGP group	240.13 ± 6.48	157.73 ± 9.67	124.96 ± 2.46
	IGP group	237.09 ± 9.32	155.40 ± 7.93	125.22 ± 4.05
	Statistics	1.320	0.871	0.259
	P value	0.193	0.388	0.797
ALP (U/L)	EGP group	164.45 ± 2.84	145.46 ± 3.19	93.91 ± 4.60
	IGP group	163.35 ± 3.12	143.67 ± 3.19	92.36 ± 4.04
	Statistics	t = 1.281	t = 1.967	t = 1.259
	P value	0.206	0.055	0.214

EGP: Extrathecal Glissonean pedicle transection; IGP: Intrathecal Glissonean pedicle transection; Post-op: Postoperative; TBIL: Total bilirubin; ALP: Alkaline phosphatase; AST: Aspartate aminotransferase.

Comparison of occurrence of complications

No perioperative death was noted in both groups. There was 1 case of postoperative hemorrhage in the EGP group and 1 case of bile leakage in the IGP group. Postoperative pleural effusion was reported in three cases in both groups. The pooled incidence of complications was 16.67% and 16.0%, respectively, in the EGP group and the IGP group, showing not statistically significant the difference (P = 0.625).

Comparison of follow-up findings

All the 49 HCC patients were followed up after surgery (range: 11.2-53.3 months; median: 36.4 months). The 1- and 3-year DFS rates were 90.5% and 66.7% in the EGP group and 84% and 64% in the IGP group. The 1- and 3-year OS rates were 91.7% and 79.2% in the EGP group and 96% and 76% in the IGP group. No significant difference was noted in terms of DFS and OS rates (Figure 2).

Figure 2 Kaplan-Meier survival curves after surgery in the two groups. A: Comparison of postoperative disease-free survival rates between the two groups; B: Comparison of postoperative overall survival between the two groups. EGP: Extrathecal Glissonean pedicle transection; IGP: Intrathecal Glissonean pedicle transection.

DISCUSSION

Laparoscopic left hemihepatectomy has become the gold standard for the treatment of left liver cancer in recent years due to its advantages including smaller surgical trauma, lower incidence of complications, and faster postoperative recovery than traditional open left hemihepatectomy[6]. However, laparoscopic hepatectomy is inherently flawed by the difficult-to-control bleeding. The Pringle maneuver, a traditional method for blocking hepatic inflow during laparoscopic left hepatectomy[7]. can effectively control intraoperative bleeding and provide a clear surgical vision. However, patients with liver cancer often have varying degrees of cirrhosis and compromised basic liver function. The use of total hepatic inflow occlusion technology, which simultaneously blocks the blood flow of the left and right hemispheres, can lead to long-term hypoxia of hepatocytes, causing irreversible damage to hepatocytes and increasing the risk of postoperative liver failure[8]. In order to alleviate the ischemia-reperfusion injury of liver tissue caused by intraoperative total hepatic vascular exclusion, Kimura et al[9] proposed a selective hemihepatic blood flow blockade method, which laid the theoretical foundation for anatomic liver resection. Wang et al[10] had systematic review selective hemihepatic blood flow blockade method during hepatectomy. Studies have shown that portal basin-based anatomical hepatectomy offers improved perioperative outcomes and oncological benefits compared to non-anatomical resection methods, better adhering to the principles of radical tumor resection[11,12]. Consequently, the Glisson pedicle regional hepatic inflow blocking technique is increasingly employed in laparoscopic hepatectomy procedures.

In the present study, laparoscopic anatomical left hemihepatectomy was performed using the Glisson’s pedicle transaction methods. Among them, 24 cases were performed by extrathecal method and 25 cases by intrathecal method, all of whom underwent laparoscopic anatomical hepatectomy. No perioperative deaths or severe complication was noted in both groups. The EGP group had significant advantages in the pedicle transection time and operation time over the IGP group. In fact, the intrathecal method requires the exposure and dissection of hepatic artery, portal vein, and bile duct in the Glisson sheath, which are quite time-consuming. Additionally, dissecting the Glisson sheath during laparoscopy can increase the risk of significant bleeding and bile leakage, as it may cause injuries to the portal vein wall and short hepatic portal vein due to the restricted visualization and operational space[13]. In contrast, the extrathecal approach allows direct dissection of the hepatic pedicles after the hilar plate is lowered, which greatly simplifies the process of transecting the hepatic pedicles and reduces the risks and complexity of the surgery, making it more practical and safer to perform the procedure using a laparoscope[14,15]. As regional hepatic inflow occlusion techniques, both extrathecal and intrathecal approaches can ensure the normal blood supply to the remaining liver and alleviate ischemia-reperfusion injury; meanwhile, they can effectively block blood flow in the tumor-bearing portal territory, which is important for achieving precise liver resection, ensuring oncological benefit, and reducing postoperative complications[16,17]. Bleeding during parenchymal dissection is primarily due to blood reflux from hepatic venous branches[18]. Therefore, there were no significant differences between the two groups in terms of postoperative complications, postoperative hospital stay, postoperative liver function markers, intraoperative bleeding, and postoperative DFS and OS rates.

Although the extrathecal approach can improve surgical efficiency, it necessitates a comprehensive grasp of the anatomical features of Laennec membrane and proficiency in delicate intraoperative dissection techniques, yielding a long learning curve. The Laennec membrane is a dense fibrous layer that overlies the subserous membrane and envelops the bare area of the liver. It not only exists on the surface of the liver but also extends into the liver, creating a potential anatomical gap between the liver parenchyma and the Glisson’s pedicle and the hepatic vein. Thus, the Laennec membrane can be used as an anatomical layer for the separation of the Glisson pedicle[19,20]. When descending the hepatic portal plate, the connective tissue at the portal plate can be opened with a HIFU firstly. Then, blunt separation can be performed along the Laennec membrane between the liver pedicle and the liver parenchyma with a separation device, and the short hepatic portal vein and bile duct can be directly dissected by titanium clip or HIFU as appropriate. Both silk sutures and bipolar electrocoagulation can be considered in case of bleeding. When the amount of bleeding is large, the first hepatic hilum can be blocked to facilitate the hemostasis of the bleeding site, which can be maintained until the entire liver pedicle is dissected. Notably, the intrathecal approach can be more suitable and safer when there are anatomical variations, tumor invasion into the secondary pedicles, or conditions such as stones or substantial dilation and deformation of the secondary pedicles[21]. The Glisson system has many anatomic variations such as the draining of right posterior pedicle into the left pedicle or into the area below the confluence of the pedicles[22], and injuries to these variations can have catastrophic consequences. Thus, these variations must be identified before pedicle dissection during an intrathecal or extrathecal procedure. Strict imaging evaluations such as abdominal CT, magnetic resonance cholangio-pancreatography, and three-dimensional reconstruction before surgery is important to identify the variations in the Glisson system and guide the selection of appropriate liver pedicle occlusion approach[23]. In our center, the "Glisson pedicle-first approach" was used, during which the left liver pedicle was ligated to occlude the blood supply to the left liver, and hepatic parenchymal dissection was performed after the ischemic zone was identified, thus lowering the risk of hematogenous or iatrogenic dissemination of tumors caused by liver extrusion and movement, which is more in line with the principles of oncology surgery[24].

CONCLUSION

In summary, both extrathecal and intrathecal Glisson approaches are feasible and safe in laparoscopic resection of left HCC, with no significant difference in oncological benefit. For operators who are proficient in laparoscopic surgeries, the extrathecal approach may be preferred as it simplifies the liver pedicle transection, shortens the operation time, and improves the surgical efficiency. However, the present study was limited by its single-center data analysis, and multi-center large-sample analyses are still required.