Laparoscopic Liver Resection: A Review of Current Status

Short-term and long-term outcomes as well as oncologic safety of LLR used in patients with hepatocellular carcinoma or colorectal liver metastases compared with OLR

In the early world review of 2804 LLR cases reported by Nguyen et al. ³ in 2009, 50% were for malignant tumors, 45% were for benign lesions, and 1.7% were for live donor hepatectomy. Of the reported cases, conversions from laparoscopic to OLR and from laparoscopic to hand-assisted approach were 4.1% and 0.7%, respectively. Overall mortality was 9 of 2804 patients (0.3%), morbidity was 10.5%, and no intraoperative deaths were reported. The 5-year overall survival (OS) and disease-free survival (DFS) rates after LLR for hepatocellular carcinoma (HCC) were 50%–75% and 31%–38.2%, respectively.

The 3-year OS and DFS rates after LLR for colorectal liver metastases (CRLM) were 80%–87% and 51%, respectively. Recently, Ciria et al. ⁵ analyzed short-term outcomes from a total of 9527 LLR cases performed worldwide. Of the cases, 65% were for malignancy and 35% were for benign indications. The mortality was 0.4%. LLR had significantly less complications, transfusions, blood loss, and hospital stay compared with OLR. The two largest reviews on LLR confirmed growing safety in selected patients and trained surgeons' hands.

While there are no published prospective randomized controlled trials on the oncologic safety comparing LLR with OLR for HCC and CRLM, there are two recent multi-institutional Japanese studies that compared perioperative and long-term outcomes of LLR with OLR for HCC and CRLM by means of propensity score matching (PSM).

Takahara et al. ⁶ analyzed long-term prognosis of LLR and OLR for HCC with 387 patients in each group and PSM was generated with preoperative characteristics, tumor features, extent of liver damage, and extent of resection. Median observation period in the LLR group was 46.7 months and in the OLR group was 51.7 months. No significant differences were observed in cumulative 1-, 3-, and 5-year OS and DFS rates between the two matched groups. Perioperative outcomes showed less median blood loss, shorter postoperative hospital stay, and less complication rate in the LLR group.

Beppu et al. ⁷ clarified long-term survival of LLR compared with OLR in patients with CRLM as 1:2 propensity score to match 171 LLRs to 342 OLRs and the matched factors included preoperative levels of CEA and CA19-9; primary tumor differentiation; pathological lymph node metastasis; number, size, location, and distribution of hepatic lesions; existence of extrahepatic metastasis; extent of liver resection; total bilirubin and prothrombin activity levels; and preoperative chemotherapy. The median follow-up was 42 months in the LLR group and 49 months in the OLR group. Five-year rates of OS and DFS did not significantly differ. The R0 resection rate was similar. These two articles are the largest published studies using PSM for supporting the oncologic safety of LLR for HCC or CRLM and confirming satisfactory perioperative outcomes. ⁸

Data on the safety and learning curve for LMH

The standard definition of LMH is three or more hepatic segments removed. There was recognition at the Second International Consensus Conference that certain LLRs presented an increased degree of difficulty that were not considered LMH by the traditional definition. This includes resection of lesions in the posterosuperior hepatic segments (I, IVa, VII, VIII).^1,2 The surgical complexity and difficulty of these areas for LLR are contrasted with left lateral sectionectomy (LLS) and anterior segments IVb, V, VI, which are ideal for surgeons beginning their experience in LLR. In fact, difficulty of LLR is determined by various factors, including tumor size, tumor location, proximity to major vessels, severity of fibrosis, and extent of liver resection.^2,12

Dagher et al. ¹³ reported 210 LMHs in an international multicenter study containing 136 right and 74 left hepatectomies. The operations were carried out by total laparoscopy in 43% of patients and for malignant disease in 54% of patients. The median blood loss was 300 mL, mean operative time was 250 minutes, median tumor size was 5.4 cm, R0 margin rate was 97%, and overall conversion rate to open surgery was 12.4%. The postoperative mortality was 1%, liver-specific morbidity was 8.1%, and general complication rate was 13.8%. Gayet et al. reported total laparoscopic right hepatectomy ¹⁴ and laparoscopic right hepatectomy combined with resection of inferior vena cava. ¹⁵ Cheek et al. ¹⁶ analyzed the published cases of LMH reporting operative time, blood loss, transfusion, postoperative morbidity, and oncologic outcomes, which supported the safety of LMH. While not widely adopted, LMH has become a standard procedure in specialized hepato-pancreatico-biliary (HPB) centers in carefully selected patients.

Surgeons should be comfortable performing minor LLR before taking on LMH.^12,17–20 Vigano et al. ¹⁷ showed that the learning curve for LLR is about 60 cases. Nomi et al. ¹⁸ used cumulative sum (CUSUM) method to evaluate the learning curve for 173 cases of LMHs containing left hepatectomy in 28 patients, left trisectionectomy in 9 patients, right hepatectomy in 115 patients, right trisectionectomy in 13 patients, and central hepatectomy in 8 patients. The learning curve comprised three phases: an initial phase of 45 patients, an intermediate phase of 30 patients, and a final phase of 98 patients. The comparison of three phases showed that median operative time, blood loss, conversion rate, and length of stay were significantly improved in phase 3 compared to phase 1. They concluded that 45 standard LMHs were required to overcome initial learning curve and that over the next 30 cases, mastery of more complex, technically demanding, and less standardized major hepatectomy was achieved. However, this study came from one of the most experienced LLR surgeons, and other centers with less experience should be cautious to apply these conclusions.

Brown et al. ¹⁹ performed a literature review of single- and multi-institution studies examining the learning curve of LMH and concluded that LMH had a learning curve of 45–60 cases compared to other complex laparoscopic techniques. There is no direct evidence that hand-assisted and hybrid technique can be used to overcome initial learning curve of LMH; however, these two methods have the theoretical advantage of controlling bleeding and decreasing conversion rate to open surgery. Total LMH is technically demanding and requires experienced HPB surgeons.^19–23

Different surgical approaches to major hepatectomy and difficulty areas including caudate and posterosuperior hepatectomy

The surgical approach used in LLR mainly is a caudal approach that differs from the anterior approach, which is used for large tumors during open hepatectomy with parenchymal transection before liver mobilization.^2,24–28 The caudal approach is suitable for laparoscopy with visual angle that improves exposure around the right adrenal gland and inferior vena cava. It also greatly facilitates identification of the Glissonian pedicle at the hilar plate and Laennec's capsule, which is essential for controlling hepatic inflow and outflow if necessary. In addition, caudal–cranial transection of hepatic parenchyma can better identify and handle intraparenchymal structures. Laparoscopic hemihepatectomy, trisectionectomy, and caudate hepatectomy are usually performed with this approach.

Cai et al. ²⁶ reported laparoscopic caudate hepatectomy in four patients and combined caudate with left hemihepatectomy in seven patients using this caudal approach. Conversions to open surgery were required for two patients and two complications occurred, one was pleural effusion and another was intra-abdominal infection. Chen et al. ²⁸ reported laparoscopic caudate hepatectomy for malignant tumor using a caudal approach in eight cases. The average operative time was 254 minutes (range 210–345 minutes), estimated blood loss was 202 mL (range 10–1000 mL), and average length of postoperative hospital stay was 6.9 days (range 4–11 days). There were no perioperative complications and mortality in the series.

Another LLR approach is the superior and lateral approach with use of intercostal or transthoracic trocars.^29–31 Xiang et al. ²⁹ performed LLR in 56 patients with lesions in posterosuperior segments (I, IVa, VII, and VIII) using the superior and lateral approach. Patients are set in the supine, dorsal elevated position, and the operating table is tilted leftward by 15°–45° according to the surgical requirements. Trocars are distributed around the lesions liver lobe in a fan-shaped pattern through the abdomen. Mean operative time was 218 minutes, blood loss was 296 mL, transfusion rate was 16.1%, conversion rate was 17.9%, postoperative complication rate was 16.1%, and no serious postoperative complications occurred. Ishizawa et al. ³⁰ also performed laparoscopic segmentectomy of segments VII and VIII using this approach. Patients are placed in the left lateral decubitus position with right arm suspended and three trocars are placed in the right upper quadrant below the subcostal margin. Another two trocars are inserted through the diaphragm in the same intercostal space under the direct visualization of transabdominal laparoscope. The roots of right hepatic vein and middle hepatic vein are fully exposed by this lateral approach.

Ogiso et al. ³¹ combined the lateral and abdominal approach for laparoscopic segmentectomy VII and VIII. LLR using a combined approach is performed in deep hepatic parenchyma more frequently, larger median tumor diameter, and greater median weight of excised parenchyma compared to abdominal-only approach. This approach provides an excellent view and short access to the dome area. Bleeding is effectively controlled because the thin vascular branches of right and middle hepatic veins are well identified in this approach. Furthermore, portal pedicles are recognized deep in parenchyma of segments VII and VIII and are clipped before their division more easily than by the other approach.

In these difficult areas, hand-assisted and hybrid techniques can be performed as well. These two methods are beneficial for managing intraoperative difficulties that are encountered, including fully exposing operative location, controlling hemorrhage in parenchymal transection, and extracting large specimen so that the possibility of conversion to full open surgery can decrease.^2,32,33

Comparison between individual and Glissonian approach to hilar structures

In laparoscopic hemihepatectomy, an extrahepatic hilar dissection to isolate and divide the hepatic artery, portal vein, and hepatic duct branch is usually a technique performed by many laparoscopic surgeons, although this technique can be time-consuming. ²⁷ On the contrary, a Glissonian pedicle approach is an important alternative technique if it is applied appropriately by experts with knowledge of liver anatomy and anatomic variations.

Machado et al.^34–36 reported laparoscopic hemihepatectomy, mesohepatectomy, and segmentectomy with intrahepatic Glissonian access. This technique can reduce operative time with safety and efficacy; however, this approach may potentially injure small Glissonian or hepatic venous branches with laparoscopic vascular clamp and stapler splitting hepatic parenchyma. Cho et al. ³⁷ reported laparoscopic anatomic liver resection in 27 patients using an extrahepatic Glissonian pedicle transection. Glissonian pedicles were encircled en bloc extrahepatically in 61 cases, including left, right, medial, right anterior and posterior, and lateral Glissonian pedicle, with no serious bleeding or injury reported.

The disadvantage of extrahepatic Glissonian pedicle transection is potential risk of injury or stenosis to the contralateral hepatic duct and bleeding in cirrhotic patients. Currently, selection of an individual hilar dissection versus the Glissonian approach is up to the surgeon's preference and expertise, as is the case with hemihepatectomy during OLR. ²

RALR versus OLR and LLR

RALR using the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) involves four robotic operating arms and a surgeon site equipped with 3D visualization. RALR may overcome inherent visual and ergonomic limitations of laparoscopy, allowing surgeons to perform advanced laparoscopic procedures with greater ease.^38,39 Kingham et al. ⁴⁰ compared 64 RALR to 64 matched patients who underwent OLR. The robotic group had shorter operative time, lower blood loss, less frequently used Pringle maneuver, and shorter length of stay. There was no significant difference in the extent of liver resection, tumor number, tumor size, specimen resection margin, and postoperative complication rate.

As for the comparison between RALR and LLR, Tsung et al. ⁴¹ retrospectively matched patients who underwent RALR and LLR in a 1:2 ratio based on background liver disease, extent of resection, diagnosis, American Society of Anesthesiologists (ASA) score, age, body mass index (BMI), and gender. The analysis showed no significant differences in blood loss, transfusion rate, R0 negative margin rate, postoperative peak bilirubin, postoperative intensive care unit admission rate, length of stay, and 90-day mortality. Patients who underwent RALR had significantly longer operative time (median: 253 vs. 199 minutes) and overall room time (median: 342 vs. 262 minutes) compared with LLR; however, an increased percentage of major hepatectomy performed with RALR was observed. Qiu et al. ⁴² reported a meta-analysis involving 776 MILR patients, of whom 254 underwent RALR and 522 underwent LLR. There were no significant differences in blood loss, hospital stay, postoperative overall morbidity, and surgical margin status between RALR and LLR; however, RALR had a longer operative time and greater cost. In summary, RALR is being used by some groups for LLR; however, cost and learning curve remain important issues.^39,42

Current status of laparoscopic LDH in living donor liver transplantation

Since initial reports of living donor liver transplantation (LDLT) in 1989, ⁴³ this technique had been an alternative for some patients with end-stage liver disease due to shortage of deceased donor organs. This is especially important in Asian countries where deceased donor organ rates are the lowest in the world due to cultural, religious, and other factors. ⁴⁴ Cherqui et al. ⁴⁵ in 2002 reported the first laparoscopic left lateral sectionectomy (LLLS) for adult to child LDLT (A-C LDLT). This technique has definite advantages, including less wound morbidity and faster recovery, over conventional open surgery. Whether the availability of a minimally invasive live donor approach actually increases willingness to serve as a live donor remains unknown.

Subsequently, Soubrane et al. ⁴⁶ compared LLLS with OLR in A-C LDLT and showed significantly lower blood loss and longer operative time in the LLDH group. Similarly, Kim et al. ⁴⁷ showed significantly shorter hospital stay and time to oral diet in LLDH. Scatton et al. ⁴⁸ analyzed 70 donors, including 67 who underwent LLLS and 3 who underwent laparoscopic left hepatectomy. The patient and graft survival rates for pediatric recipients were 95% and 92% at 1 year, 95% and 88% at 3 years, and 95% and 84% at 5 years, respectively. These results validate safety and reproducibility of this procedure in specialized centers; however, expansion to other centers is still scarce. Soubrane et al. ⁴⁹ compared short-term donor outcomes of LLLS for A-C LDLT with laparoscopic donor nephrectomy (LDN) using comprehensive complication index, for which LDN is the standard approach in kidney donors. After PSM, LLLS and LDN have similar short-term donor outcomes which is that the safety and feasibility of this procedure are revalidated.

With the improvement of LMH, the techniques of laparoscopic left hemihepatectomy and right hemihepatectomy for adult to adult LDLT (A-A LDLT) have been feasible; however, reports of this technique are relatively limited in contrast with LLLS for A-C LDLT. Laparoscopic-assisted, hybrid method, with or without hand assistance, and pure laparoscopic living donor major hepatectomy have showed less pain and shorter hospital stay compared with open surgery^50–54 ; however, donor safety remains a prime concern and it is unknown if it will gain broad acceptance.^2,55

Feasibility and benefits of laparoscopic ALPPS

In 2007, Dr. Schlitt from Regensburg, Germany, performed the first ALPPS on a patient with perihilar cholangiocarcinoma. ⁵⁶ Since then, this technique has drawn attention and much debate among liver surgeons. Schnitzbauer et al. ⁵⁷ presented ALPPS showing an increase in the future liver remnant (FLR) volume of 74% in a much shorter time of 9 days compared with portal vein embolization (PVE), which is a standard technique used clinically in patients with insufficient FLR that typically yields an increase in FLR volume of 12% in 4–8 weeks.^58,59 In addition, the longer time period required for PVE-induced hypertrophy has the theoretical risk of tumor progression.^60,61 However, morbidity from ALPPS was high at 33%–64% compared with 16% after PVE. ⁵⁹ Machado et al. ⁶² successfully performed totally laparoscopic ALPPS in a woman with multiple and bilobar CRLMs. The reduced adhesion caused by laparoscopic one-stage procedure greatly facilitated the success of two-stage procedure. Subsequently, Xiao et al. ⁶³ performed totally laparoscopic ALPPS for treatment of cirrhotic HCC with satisfactory short-term efficacy.

ALPPS offers enhanced hypertrophy in patients with inadequate FLR; however, morbidity and mortality related to ALPPS have to be considered.^64,65 Several modifications to this technique have been described to replace hepatic parenchyma transection to avoid bile leakage from split hepatic parenchyma after one stage, which is one reason for morbidity/mortality of the initial description. ⁶⁶ These modifications have been performed by a pure laparoscopic as well. Gall et al. ⁶⁷ performed laparoscopic ligation of right portal vein and then radiofrequency ablation along the demarcation between left and right lobe in the first stage, which could significantly increase the FLR volume by a median of 62.3% in a much shorter length of time (mean = 21.8 ± 9.4 days) than by PVE. Gringeri and colleagues ⁶⁸ successfully applied completely laparoscopic microwave ablation to replace liver parenchyma transection in the first stage of ALPPS. Cai et al. ⁶⁹ used round-the-liver ligation to replace in situ splitting of liver in one stage and FLR volume increased rapidly. Laparoscopic techniques are potentially advantageous for the first phase of ALPPS, but additional larger studies are required before it can be considered standard of care.