© 2013, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(13)60040-5

 

Contributors: QNS, LYH and DJH proposed the study. QNS and LYH wrote the first draft. QNS, LYH, CSW and RV polished the manuscript. All authors contributed to the design and interpretation of the study and to further drafts. DJH is the guarantor.

Funding: This work was supported by grants from the National Natural Science Foundation of China (81172095, 81171135 and 81200324), Bureau of Health Medical Scientific Research Foundation of Hainan Province (Qiongwei 2012 PT-70), China Postdoctoral Science Foundation funded project (2012m521875).

Ethical approval: Not needed.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

 

 

BACKGROUND: Liver surgery has gone through the phases of wedge liver resection, regular resection of hepatic lobes, irregular and local resection, extracorporeal hepatectomy, hemi-extracorporeal hepatectomy and Da Vinci surgical system-assisted hepatectomy. Taking advantage of modern technologies, liver surgery is stepping into an age of precise liver resection. This review aimed to analyze the comprehensive application of modern technologies in precise liver resection.

 

DATA SOURCE: PubMed search was carried out for English-language articles relevant to precise liver resection, liver anatomy, hepatic blood inflow blockage, parenchyma transection, and down-staging treatment.

 

RESULTS: The 3D image system can imitate the liver operation procedures, conduct risk assessment, help to identify the operation feasibility and confirm the operation scheme. In addition, some techniques including puncture and injection of methylene blue into the target Glisson sheath help to precisely determine the resection. Alternative methods such as Pringle maneuver are helpful for hepatic blood inflow blockage in precise liver resection. Moreover, the use of exquisite equipment for liver parenchyma transection, such as cavitron ultrasonic surgical aspirator, ultrasonic scalpel, Ligasure and Tissue Link is also helpful to reduce hemorrhage in liver resection, or even operate exsanguinous liver resection without blocking hepatic blood flow. Furthermore, various down-staging therapies including transcatheter arterial chemoembolization and radio-frequency ablation were appropriate for unresectable cancer, which reverse the advanced tumor back to early phase by local or systemic treatment so that hepatectomy or liver transplantation is possible.

 

CONCLUSIONS: Modern technologies mentioned in this paper are the key tool for achieving precise liver resection and can effectively lead to maximum preservation of anatomical structural integrity and functions of the remnant liver. In addition, large randomized trials are needed to evaluate the usefulness of these technologies in patients with hepatocellular carcinoma who have undergone precise liver resection.

 

 

KEY WORDS: precise liver resection; anatomy; parenchyma transection; down-staging treatment

 

In 1888, Lang Enbuch, a German surgeon, successfully completed the world's first elective liver resection which inaugurated the modern liver surgery.^[1] Over the past century, liver surgery has gone through the phases of wedge liver resection, regular resection of hepatic lobes, irregular and local resection, extracorporeal hepatectomy, hemi-extracorporeal hepatectomy and Da Vinci surgical system-assisted hepatectomy.^{[2, 3]} During the past two decades, operation advances pursuit more than complete irradiation of lesions and shorten operation time. A multi-dimensional and comprehensive measurement combining minimal harm to the patients, maximal protection of the organ, and the best rehabilitation has been in considerations. Modern technologies also accelerate the transformation from traditional extensive surgical models to modern precise ones.

 

 

Relying on the current highly-advanced biomedicine and information technology, precise liver resection covers a new conception of liver surgery and technologies. While trying to completely eliminate target lesions, precise liver resection aims to keep the largest possible anatomical structural integrity and liver remnant volume, control operation hemorrhage and systemic tissue damage, and finally gain the best rehabilitation in patients. Instead of emphasizing advanced surgical technology, or a standardized liver resection model that is suitable to all cases, precise liver resection combines, highly precisely and validly, comprehensively and optimally, a series of modern scientific theories and technologies and traditional surgical methods. Tailored for individuals, precise liver resection includes modern imaging techniques, quantitative measurement of hepatic reserve function, digital surgical platform, improvement of traditional surgeries and, the elaboration of nursing and multi-disciplinary cooperation during operation, as well as the fast track surgery after surgery.

 

 

The anatomical study of intrahepatic vascular and biliary systems parallels with the evolution of hepatic surgeries.^[4] As a result, the breakthrough of hepatic surgeries lies in the mastery of the complexity and variability of the liver and its vascular structure.

 

Modern medical imaging technology has helped hepatic surgeons to see the intrahepatic anatomical structure and the lesion much clearer. The combined use of ultrasound, computer tomography (CT), magnetic resonance imaging (MRI) and other imaging technologies could precisely evaluate the range of lesions, stage of malignant tumors and type of benign ones, and clarify the distribution, course, variation of complicated intrahepatic vascular systems and their adjacent relationship with the lesions.^[5-7] This method could provide important information for deciding the resectability of hepatic lesions, operative indications, and surgical plans. High-resolution imaging tools such as CT angiography, CT arterial portography (CTAP), high-field MRI, and ultrasound imaging can detect minimal hepatic carcinoma with a diameter smaller than 10 mm, which marks a remarkable accuracy in the precision of hepatic lesion evaluation.

 

Modern hepatectomy is based on Couinaud's liver segmentation, which depends on the hepatic vessel anatomy, so the imaging study of hepatic vessels is significant for liver surgery. In the past, hepatic anatomical knowledge was acquired by slitting or vessel casts.^[8] As digital medicine is based on great progress in computer science and information technology, we can quantitate diseases by digital imaging. Because of the advancement of CT and MRI, the 3D reconstruction of the hepatic vessel can be used to analyze the preoperative risk.^{[9, 10]} Compared to the conventional two-dimensional gray scale images captured by CT or MRI, the reconstructed 3D image exhibits the liver parenchyma, hepatoma, and hepatic vessels from different angles with pseudo-color. Thus the adjacent relationship of hepatic and intra-hepatic vessel systems can be amplified and tracked, and quantitative studies for clinical use can be performed immediately.^[10] With the 3D image system, analysis of the hepatic vessel system can be made before hepatectomy, while imitating the liver operation procedure. The 3D image system can also help to make risk assessment, identify the operation feasibility, and confirm the operation scheme.^[10] At present, the 3D reconstruction and visualized model of the hepatic vessel system has been used in clinical practice.

 

 

Liver reserve function test is dependent on the hemi-quantitative method of Child-Pugh grade. In recent years, indocyanine green angiography (ICG) excretion test, normal liver biochemical test and Child-Pugh grading have been considered as the major criteria for evaluating liver reserve function. Liver reserve function detected by the above methods can be used to estimate the safety level of liver resection.^[11]

 

The safety level of liver resection should not be measured by the resected volume, but by the necessary functional mass left over. It is generally believed that the remnant volume should be at least 25%-30% of the entire liver.^[12] Clinical data from Asia, Europe and the USA show that resection volume in patients with chronic liver diseases can be predicted by Child-Pugh grade, portal artery hypertension, and ICG excretion test in combination. Child C patients are restricted from any liver resection. Child B patients with portal artery hypertension or ICG R15 clearance less than 30% are suitable for subsegmentectomy or enucleation. For Child A patients without portal artery hypertension or ICG R15 clearance less than 10%, 10%-20% and 20%-30%, the remnant liver volume should be at least 40%-50%, 60%-70%, and 70%-80% of the liver mass respectively.^[13]

 

 

Accurate calculation of remnant liver volume is of vital importance for the safety of liver resection. Remnant liver volume is estimated via preoperative CT/MRI images and operative detection of liver tumor. At present, the entire liver volume, the volume to be resected, and the remnant liver volume can be precisely calculated through delineation on the 2D images of the picture archiving and communication system (PACS)^[14] and computerized automatic accumulation. Computer-aided 3D re-construction based on 2D images can measure every liver segment, and precisely check the blood supply of any visible vessels. Comparison of 2D and 3D CT images with post-operative liver specimen can show great conformity with the real volume, and there is no statistical difference between 2D and 3D measurements in irregular and local resection. 3D imaging is advantageous in volume calculation of the region dominated by every vessel of the liver segments or sub-segments. Consequently, 3D imaging is feasible for pre-operative quantitative evaluation of ischemia/congestion of the liver caused by liver resection and could determine the reserved function more precisely.^[15]

 

 

Through virtue operations by a computer-aided surgical planning system, the blood vessels of interest and its branches can be quantified, while predicting the possible areas and scopes of liver ischemia and congestion. Then we could determine the appropriate region for resection and manage the involved vessels. To better protect the structural integrity of the liver vasculature while separating the surface of the parenchyma, we need to have adequate tumor-free resection margins, preserve functional liver parenchyma, resect along the interspace between areas with less vascular structures, and avoid damage to the vascular structure in the area left over. In multi-frame 2D image analysis or virtual surgery based on 3D image restructuring, the best split surface can be determined by comparing the margin status, the volume of the resected region, the preserved region and the integrity of its structure.

 

 

In the past, vascular reconstruction was dependent on the diameter of the hepatic vein. The reconstruction was considered necessary when the diameter of the transected hepatic vein was bigger than 5 mm. Currently, hepatic venous reconstruction is based on vascular assessment. Through hepatic artery blocking experiments and intraoperative ultrasound, liver congestion can be assessed by naked eye and blood flow. If the residual liver volume is smaller than 30% of the standard liver volume after resection, hepatic venous reconstruction is needed.^{[16, 17]}

 

Near infrared spectroscopy (NIRS) can be used to quantitate the degree of liver congestion, if the level of residual hemoglobin in the right anterior lobe of the donor liver is more than 70% before irrigation, liver congestion is serious and hepatic venous reconstruction is indicated. If the level of residual hemoglobin is 40%-70%, there are a medium liver congestion, a high level of bilirubin, and a temporary higher level of transaminase after surgery.^[18]

 

 

Consistent with precise liver resection, anatomical resection of liver segments can effectively clear the lesions and protect the structural integrity of the reserved liver. This theory applies to the surgical treatment of hepatocellular carcinoma (HCC). Takasaki et al^[19] ligated the hepatic pedicle in the hepatic segment, observed the areas of hepatic ischemia, and finally determined the resection area. In the process of hepatic parenchyma transection, however, the cross surface could hardly be grasped because of bleeding. In 2008, Aoki et al^[20] injected ICG into the liver segment and then resected the segment under a microscope. As the fluorescence lasts long, this method improves the accuracy of surgery.^[20]

 

Our technique was named as puncture skill, a modification according to Makuuchi's study.^[21] Briefly, we injected methylene blue into the target Glisson sheath which was ligated after staining. Advantageously, the target liver segment can keep the staining for a long time due to the ligation, and the staining can be clearly distinguished even with bleeding interference in liver parenchyma transection. Our technique ensures the accuracy of surgery.^[22]

 

 

Pringle maneuver so far is still the most common and effective temporary method to block hepatic blood inflow. Intermittent Pringle maneuver is generally used to reduce damages caused by hepatic ischemia-reperfusion. Recently, techniques of selective hepatic blood inflow blockage have been established. Makuuchi et al^[23] reported hemihepatic blood inflow occlusion by dissociating the hepatic artery, portal vein and bile duct branches from the Glisson sheath and by ligating and resecting lateral hepatic vessels. Takasaki et al^[24] ligated the extrahepatic Glisson pedicle and thus, the blood flow in the corresponding liver segments or lobes was blocked. In addition, Shimamura et al^[25] created another method, they punctured the portal vein of the target hepatic liver segment and then, transplanted a balloon catheter into it, and thereby hepatic blood inflow was blocked when the balloon was inflated.

 

All of the new methods are not universally accepted. Pringle maneuver is still the oldest and simplest way and favored by many surgeons. This maneuver can be used in conjunction with afferent or total devascularization of the part of the liver to be resected and with extraparen-chymal control of the major hepatic veins.^[26-28]

 

Another way is to decrease the central venous pressure (<5 cmH₂O). This technique applies to hepatec-tomy cases with normal liver parenchyma and sufficient volume of the preserved liver for functioning. In patients with serious liver parenchymal damage and insufficient volume of the preserved liver function, resection with hepatic blood flow unblocked or selective half-hepatic blood blockage can be considered. In difficult liver resection, where expected blockage time of liver blood flow breaks the limit of liver ischemia, liver resection under total hepatic vascular isolation and cold perfusion can be adopted. If there is a need for resection and reconstruction of the liver because of burdens on the major hepatic veins and hepatic inferior vena, liver resection under total hepatic vascular blockage or in vitro resection may be necessary.

 

 

At present, a series of mature approaches have been established to deal with hemorrhage in liver resection. Because of the existence of blood-vessel-free regions between the anatomical gaps of liver segments and liver lobes, liver parenchyma transection in these gaps can help reduce operative hemorrhage in hepatectomy. Exquisite equipments for liver parenchyma transection, such as cavitron ultrasonic surgical aspirator,^[29] ultrasonic scalpel,^[30] Ligasure^[31] and Tissue Link^[32] can also be used to reduce hemorrhage in liver resection, or even to perform exsanguinous liver resection without blocking hepatic blood flow. In the superficial regions of the liver without important vascular structures, clamp crushing and electric coagulation can transect liver parenchyma. Direct liver parenchyma transection can be done by ultrasonic hemostasis knife, PK knife transection and other thermal coagulation. Even in the hepatic portal region near the important vascular structures, exquisite equipments such as ultrasonic scalpel also make the precise operation possible. These equipments combined with electric coagulation help to control bleeding in liver parenchyma transection.

 

These techniques facilitate the process of liver parenchymal transaction, minimize blood loss, and prevent bile leakage or fistula. It is still unclear which technique is the best for a specific procedure. An individual surgeon needs to choose his/her favorite technique according to the condition of patients, surgeon’s experience and the resources available.

 

 

In living donor liver transplantation (LDLT), resection of the donor liver is a typical application of precise liver resection. Donor liver has to match the need of the recipient in terms of integral structures and sufficient function volume. Moreover, the remnant donor liver has to have adequate compensatory function and structural integrity. There are a series of innovative technologies used in LDLT, including liver parenchyma resection with hepatic blood inflow unblocked, accurate measurement of liver volume, calculation of the minimum volume of preserved liver part, the anatomy and variation recognition of horizontal blood vessels with liver segments and bile ducts, fine vascular anastomosis and biliary reconstruction, the distribution and reconstruction of hepatic veins and their important branches. They need further investigation.

 

 

In 1988, Pichlmayr et al^[33] first reported extracorporeal hepatectomy which included liver resection and liver transplantation. This technique is used to deal with the tumor which conceals in the dorsoventral part, while invading the postcava or hepatic major veins. In the past, the tumor involving the main vessels was considered as a contraindication for surgery.^[34] At present, partial vascular resection, vascular repair and reconstruction significantly improve the operative safety, accuracy and curability.^[35] Improved hemi-extracorporeal hepatec-tomy can avoid extracorporeal venous bypass and significantly decrease the anhepatic phase and shorten the operative time.^[36] Semi-extracorporeal hepatectomy is performed under hypothermic perfusion with blockage of hepatic blood inflow. Then the liver precava and postcava are cut, and the liver is turned over. This maneuver exposed the second and third hepatic hilum much clearer and the hepatectomy can be performed easily. The operation is performed in the state of bloodless and the intrahepatic ducts are visible, hence vascular injury is reduced. In addition, injury to or tumor invasion of the main vessels can be repaired or partially resected.^[37] Venous bypass technology significantly reduces the time of hepatic ischemia.

 

In recent years, the Da Vinci surgical robot system has been introduced. This technique significantly improves the precision of hepatectomy.^[38-40] Scholars have even defined it as a new surgery era coming.^{[41, 42]}

 

Our clinical practice showed that robotic-assisted anatomic hepatectomy is safe and feasible with a lower rate of complication and conversion. The robotic surgical system may broaden the indications of laparoscopic hepatectomy, and it enables the surgeons to perform precise laparoscopic liver resection.^[40]

 

 

Intraoperative ultrasonography (IOUS) during surgery for primary and metastatic hepatic tumors identifies additional lesions and helps in determining the most optimal surgical strategy.^{[43, 44]} Lesions with a diameter greater than 2 mm can be detected by IOUS and the sensitivity is over 90%. IOUS is helpful in determining preoperative lesions, and also in detecting new lesions. Approximately 70%-80% of the newly discovered lesions are benign, including regenerative and dysplastic nodules. Contrast-enhanced ultrasonography can help to identify liver cancer, so biopsy can be done when necessary. IOUS also guides puncture biopsy, drainage, and radio-frequency ablation (RFA). In addition, IOUS provides the anatomical information about the location, range, and surrounding vessel structures of the lesion, which is significant for choosing the correct surgery scheme. In addition, IOUS helps to modify the surgical planning or re-identify the possibility of hepatectomy.^{[45, 46]}

 

IOUS helps to perform anatomic liver resection by puncturing portal vein branch near the targeted area and by injecting indigo carmine into the vessel.^[47] The stained area becomes evident on the liver surface and is marked with electrocautery. With IOUS, the relationship between the dissection plane and the tumor edge can be followed in real time, and the direction of the dissection plane can be modified when needed. Moreover, the portal vein branch is exposed and skeletonized with the hooking technique and then it is encircled with a stitch. This is visualized by IOUS. IOUS guarantees that resections, both anatomic and limited, are safe but oncologically acceptable.^[48]

 

Recently, 3D real-time ultrasound navigation, with greater feasibility and which could significantly improve the precision of operations, has been used in liver resection.^[49]

 

 

To improve the radical resection rate of malignant tumors, liver resection should follow the principle of tumor-free so as to avoid residual tumor and iatrogenic spread. First, the tumor should be resected en bloc in normal liver tissues out of the tumor mass with no tumor infiltration. For cases of malignant tumors that have encroached on major vascular structures of the liver, radical resection rate can be tremendously improved by resection and reconstruction of the liver together with blood vessels. The minor residual lesions after the resection of the major tumor can be completely removed by intraoperative/postoperative RFA, precise radiotherapy, transcatheter arterial chemoembolization (TACE), and other remedial treatments.

 

If the volume of the preserved liver is less than the minimum volume for liver function, the following means can be considered to raise the preserved liver volume for functioning and to improve the rate of radical resection:

1) Selective embolization of the portal vein in the liver segments to be resected can prompt the growth of the preserved liver so as to ensure the minimum or larger volume for liver functioning.

2) Removal of reversible factors causing liver injuries and improvement of the preserved liver function. In treating patients who require resection of a bulk of the liver accompanied by severe obstructive jaundice, preoperative selection or whole biliary drainage can help to improve liver functions.

3) Operations that save liver parenchyma and select minimum tumor-free margins, such as resection of liver segments/sub-segments, or limited and partial hepatectomy, while ensuring full removal of target lesions, help to avoid chunks of the clamp and suture of liver tissues on the cross surface.

 

In recent years, tumor capacity reduction is highly noticed internationally. Down-staging treatment of malignant tumors with wide pathological changes can narrow the scope of tumor affection and facilitate radical liver resection. Down-staging treatment is appropriate for the unresectable tumor, made the advanced tumor back to early phase by local or systemic treatment so that hepatectomy or liver transplantation could be performed. Now there are various down-staging therapies including TACE and RFA.^[50] Only 15%-20% of HCC patients are indicated for primary resection when diagnosed, and approximately 10.9%-57.1% of the HCC patients diagnosed with unresectable tumor could be successfully treated by remedial liver resection after down-staging treatment. The survival rate of these patients over 5 years was 24.9%-57%.^[51] A meta-analysis^[52] showed a significant survival rate in patients with unresectable HCC treated by TACE. RFA is safe in terms of liver function and can be performed even in patients with advanced liver failure. It is most effective for the treatment of HCC with a diameter of ≤3 cm.^[52] TACE combined with RFA is indicated for residual or satellite tumor lesions (≤4 cm). TACE is first performed to limit heat loss by convection (heat-sink effect) during RFA. TACE after RFA aims to clear up the residual viable tumor after ablation of a large HCC. ^[53]

 

 

In summary, precise liver resection includes precise preoperative planning, and sophisticated intraoperative techniques. This strategy is characterized by involve-ment of minimally invasive concept in overall therapy, from preoperative assessment to postoperative care, optimization of a series of advanced techniques and proper employment of surgical instruments in light of actual individual information. The modern technologies mentioned above are the key tools for achieving these goals, which can effectively lead to maximum preservation of anatomical structural integrity and functions of the remnant liver. Moreover, large randomized trials are required to evaluate the usefulness of these technologies in HCC patients who have undergone precise liver resection after long-term follow-up on control of complications and survival.

 

 

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