Author Affiliations: Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue BX7375 CLINICAL SCIENCE CNTR Madison, WI 53792-7375, USA (Salem AI and Winslow ER)

Corresponding Author: Emily R Winslow, MD, FACS, Assistant Professor, Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue BX7375 CLINICAL SCIENCE CNTR Madison, WI 53792-7375, USA (Email: winslow@surgery.wisc.edu)

 

© 2017, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(16)60147-9

Published online November 4, 2016.

 

 

Contributors: SAI proposed the study, performed the research, collected and analyzed the data, and wrote the first draft. Both authors contributed to the design and interpretation of the study and to further drafts. WER is the guarantor.

Funding: None.

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: With the recent advances in oncological hepatic surgery, major liver resections became more widely utilized procedures. The era of modern hepatic surgery witnessed improvements in patients care in preoperative, intraoperative and postoperative aspects. This significantly improved surgical outcomes regarding morbidity and mortality. This review article focuses on the recent advances in oncological hepatic surgery.

 

DATA SOURCES: This review includes only data from peer-reviewed articles and journals. PubMed database was utilized as the primary source of the supporting literature to this review article on the latest advances in oncological hepatic surgery. Comprehensive and high sensitivity search strategies were performed to search related studies exhaustively up till June 2016. We critically and independently assessed over 50 recent publications written on this topic according to the selection criteria and quality assessment standard. We paid particular attention to the studies published in high impact journals that address the use of the surgical techniques mentioned in the articles in well-known institutions.

 

RESULTS: Among all utilized approaches aiming at the preoperative assessment of the liver function, Child-Turcotte-Pugh classification remains the most reliable tool correlating with survival outcome. Although the primary radiological tools including ultrasonography, computed tomography and magnetic resonance imaging remain on top of the menu of tests utilized in assessment of focal hepatic lesions, intraoperative ultrasonography projects to be a powerful additional tool in terms of sensitivity and specificity compared to the other conventional techniques in assessment of the liver in the operative setting, a procedure that can change the surgical strategy in 27.2% of the cases and consequently improve the oncological surgical outcome. In addition to the conventional surgical techniques of liver resection and portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy “ALPPS” projects to be an alternative option in patients with marginally resectable tumors with an inadequate size of future liver remnant with an accepted surgical oncological outcome.

 

CONCLUSIONS: Considering the clinicopathological nature of hepatic lesions, the comprehensive assessment and proper choice of the liver resection technique in highly selected patients is associated with improved surgical oncological outcome. Patients with underlying marginal future liver remnant volumes can now safely benefit from a wider range of surgical intervention, a breakthrough that significantly improved morbidity and mortality in this group of patients.

 

(Hepatobiliary Pancreat Dis Int 2017;16:147-154)

 

KEY WORDS: liver surgery; liver neoplasms; technical aspects; oncosurgery; liver metastasis

Liver resection has long presented challenges for surgeons due to the liver’s complex anatomy, unique vasculature and need for preservation of adequate functional reserve after resection. With the advances in surgical techniques utilized in liver surgery in recent years, hepatic resection is being undertaken more often, in a wider range of disease states, and with improved outcomes. Improvements in preoperative assessment, operative technique, and postoperative care have allowed for more aggressive resections to be offered to patients with equivalent, or perhaps better, outcomes. This article reviews recent literature regarding preoperative hepatic assessment, optimization of operative conditions, and a detailed discussion on the most current techniques used for hepatic resections.

 

Both qualitative and quantitative evaluation of the liver preoperatively is of pivotal importance when planning a hepatic resection. Determination of the future liver remnant (FLR) can be done using indocyanine green (ICG) clearance rate, the lidocaine-MEGX test, or volumetrically using axial imaging. Regardless of the method chosen, it is essential to assure that an adequate volume of functional hepatic parenchyma will remain after resection.^{[1, 2]} Although volumetric measurements perform well for the majority of patients, it is important to note that patients with liver function compromised by underlying disease may have inadequate functional reserve despite preservation of an otherwise “adequate” volume. For patients with borderline FLRs (e.g. 20% of the original volume of a normal liver or 40% of the original volume of a cirrhotic liver), preoperative portal vein embolization (PVE, see below) can be considered in an effort to induce hypertrophy of the FLR up to 12% of the total hepatic volume.^[3]

 

Regarding predicting rates of morbidity and mortality of hepatic resection preoperatively, the Child-Turcotte-Pugh (CTP) classification has remained the most studied classifications in the literature that was found to correlate well with survival outcome after liver surgery. Estimates for one- and two-year survival can be made on a basis of the CTP class: 95% and 90% for class A, 80% and 70% for class B, and 45% and 38% for class C, respectively.^[4]

 

 

The use of preoperative PVE has significantly changed the approach to major hepatectomy and has made extended resections safer for patients.^[5] Percutaneous PVE is minimally invasive procedure that can be easily performed in the radiology suite with local anesthesia or under conscious sedation.^[6] PVE is most useful for patients with underlying marginal FLR volumes (i.e., FLR <20% in patients with a normal liver, FLR <30% for patients with non-alcoholic steatohepatitis, and FLR <40% in patients with cirrhosis). So it facilitates hepatectomy with much less risk of postoperative liver failure and consequently lower rates of postoperative morbidity and mortality.^[7-10] Success rates of PVE vary widely according to the underlying liver condition. While liver cirrhosis was found to have an adverse effect on PVE outcome, cholestasis and chemotherapy were not associated with worse observed outcome compared to normal liver condition.^[11] While PVE can induce up to 12% hypertrophy of the total hepatic volume, it takes a mean interval of 31 days between PVE and surgery to allow for adequate FLR.^{[3, 12]}

 

Ultrasonography (US) remains the easiest, fastest and the most non-invasive modality for liver imaging. With jaundice being a typical presentation of hepatic disease, US can determine whether this is obstructive versus non-obstructive jaundice and evaluate other possible accompanying conditions namely evidence of fibrosis or cirrhosis and the presence or absence of mass lesions.

 

Computed tomography (CT) is the standard examination for most hepatic mass lesions due to its ability to provide excellent visualization of the hepatic parenchyma and vasculature as well as to identify extrahepatic diseases. Tri-phasic thin slice CT scan of the liver is a useful dedicated technique to utilize for patients with known or suspected hepatic lesions.

 

Magnetic resonance imaging (MRI) plays a significant role in the assessment of hepatic lesions and can help in distinguishing the malignant lesions in the liver from the benign ones. The use of hepatobiliary-specific contrast agents and the acquisition of delayed imaging helps the abdominal radiology to make a well-informed assessment of the nature of hepatic lesions, even as small as 10 mm in size.^[13]

 

 

Hepatic resections can be approached in either a traditional open fashion or via a laparoscopic approach. The choice of technique depends on the surgeon’s experience, the nature, and location of the hepatic lesions and the patient’s underlying medical condition. For the open approach, the most preferred one among surgeons is a right subcostal incision which enables easy and safe access to the liver. A right subcostal incision may be extended either in the midline towards the xiphoid process or to the left side. A hybrid approach with laparoscopic hepatic mobilization followed by open surgery through a more limited incision has also been described.

 

 

IOUS is an important tool to utilize both before and during hepatic resection. The use of IOUS early in the case helps to identify any previously undetected lesions, to map the transection plane, and to determine the relevant vasculature in relation with the hepatic surface. Ferrero et al described IOUS sensitivity/specificity of 92%/97.8% compared to 63.6%/91%, 68.8%/92.3%, and 53.6%/95.8% for CT, MRI, and fluorodeoxyglucose positron emission tomography respectively.^[14] Also, in the same study surgical strategy was changed in 27.2% of the cases in light of the new findings on IOUS.^[14] Looking at the pattern of recurrence with utilizing IOUS, Santambrogio et al^[15] performed a study on 377 patients all of whom had hepatocellular carcinoma with 42% treated with hepatic resection and the remaining 58% with surgical radiofrequency ablation. All patients underwent IOUS examination. With a median follow-up period of 19.6 months, 52.2% of all patients had a recurrence, 36.5% of those recurrences were located in segments that are different from that of the primary tumor while 16% were found in the same segment as the primary tumor.^[15] The use of contrast-enhanced US in the operating room is currently undergoing investigation and may help the surgeon and the radiologists to identify small and subtle hepatic lesions more reliably.^[16]

 

Three-dimensional pre-resection planning software has been marketed in recent years to help surgeons better visualize the transection plane considering the relation to the key vasculature and the patient’s specific lesions. Although this is intuitively appealing and generates excellent images that are useful to the surgical trainee, it has not yet been shown to impact patient care and has not been incorporated into most center’s routine practice.^[17] Also, the use of image guided resections using real-time intraoperative axial imaging has been studied and utilized in some centers.^[18]

 

 

Liver mobilization is a major step that aims to provide better visualization of the hepatic pathology and to allow safer transection of the liver. Complete liver mobilization is achieved through division of the falciform, triangular and coronary ligaments; this allows freeing the liver from its attachments to the diaphragm and retroperitoneum, exposing the bare area of the liver and the short hepatic veins draining from the right liver into the inferior vena cava (IVC).

 

 

Crushing liver resection techniques have been introduced as the earliest methods utilized for isolation and division of small vessels and biliary radicals.^[19] This includes “finger-fracture” and “clamp-crush” techniques with the clamp-crush showing better hemostatic control over finger-fracture.^[19] Although it is the oldest technique in liver surgery, it is still widely used by surgeons since it is simple, inexpensive, quick and easy to learn. Several randomized controlled trials and meta-analyses failed to show superior benefit for some of the modern techniques including the vessel sealing system (LigaSure), Cavitron ultrasonic surgical aspirator (CUSA) or Hydrojet when compared to the conventional crushing techniques.^[20-22]

 

Using a broad range of ultrasonic frequencies, CUSA can fragment liver parenchymal tissue leaving structures like blood vessels and bile ducts intact. It is useful when a very-well defined transection plan is required as in cases where tumors are in proximity to major vascular structures.^[19] CUSA allows for customization of the fragmentation power according to the nature of tumor tissue. While the 24 kHz hand-piece provides fragmentation power that suits fibrous or calcified tumors, the 35 kHz hand-piece provides precision, tactile feedback, and fine control.^[23] Comparing it with the clamp-crushing, the clamp-crushing technique had the highest transection velocity (3.9±0.3 cm²/min) and lowest blood loss (1.5±0.3 mL/cm²) compared with CUSA (2.3±0.2 cm²/min and 4.0±0.7 mL/cm²).^[21]

 

Electrothermal bipolar vessel sealing (EBVS) is a technology that is based on starting a sealing cycle under a generator control, the generated electrical current travels through the vessel wall and works on creating an electromagnetic field that is capable of energizing the electrons within the blood vessels. These energized electrons release their energy as heat resulting in denaturation of the proteins found in the structure of collagen and elastin components present in the blood vessels.^[24] The power generated is enough to seal vessels with a diameter of up to 7 mm.^[25] One advantage of this system is that it performs both the parenchymal resection function along with vascular sealing at the same time; a dual function that at one time was believed to be time-saving in comparison to the gold-standard clamp-crush. However, recent randomized controlled trials comparing these two approaches failed to show an advantage of the vessel sealing system (LigaSure) over the conventional clamp-crush.^{[22, 26]} A recent randomized controlled trial by Muratore and colleges showed no differences regarding blood loss, transection time, transection speed or rates of mortality, morbidity or bile leak.^[27]

 

An additional technique that impacted the performance of liver surgery utilized radiofrequency waves to aid in the safe resection and was first introduced by Habib and colleagues in 2002.^[28] This technique uses radio waves delivered to the parenchyma at very high frequencies that may reach up to 500 kHz through various probes designed to suit different surgical conditions. The technique allows for pre-coagulation of the intended transection plane by generating temperatures up to 300 �� causing coagulative necrosis of tissues.^[29] This technique has been used in standard open surgery, in minimally invasive resections, and in CT-guided percutaneous liver ablation. A recent randomized controlled study by Li and colleagues^[30] from 2013 compared outcomes from resection of hepatocellular carcinoma in cirrhotic patients using radiofrequency-assisted parenchyma transection to gold-standard clamp-crushing technique and found the radiofrequency-assisted liver resection was associated with significantly less blood loss with no significant change in rates of morbidity.

 

In contrast to the radiofrequency-assisted liver resection, the saline-linked radiofrequency sealer depends on the transmission of 480 kHz radiofrequency energy through saline dripping from the tip of the hand-piece.^[29] Saline dripping allows for maintaining the tissue temperature at or below 100 ��, a temperature that is enough for sealing of the vessels through collagen and elastin shrinkage but not enough to cause the tissue fragmentation observed in the conventional radiofrequency-assisted liver resection.^[29] These changes on the molecular and tissue levels are believed to create better hemostatic conditions especially if an underlying liver disease is present at the time of surgery. In the controlled study by Xia and colleagues, the potential benefit of the saline-linked radiofrequency sealer was examined in cases with cirrhotic livers. They found that saline-linked radiofrequency sealer was associated with significantly less blood loss and reperfusion-related liver injury with the longer resection time being the only drawback limiting the use of this technique.^[31]

 

Water-jet dissection is a concept that has been employed in so many aspects of the recent scientific applications including surgery.^[32] This technique depends on a high-velocity current of water pointed at a small surface area allowing for high-pressure energy. Water-jet dissection minimizes vascular damage at the time of hepatic parenchymal dissection because it cuts the parenchyma, preserving the integrity of the vascular components. One drawback of this technique is that it requires manual ligation of these vascular components which is expected to prolong the time of dissection. This technique has been utilized in particular circumstances in hepatic resection, such as the procurement of a hepatic graft from a living donor.

 

Minimally invasive liver surgery is a term that describes a broad range of techniques starting from total laparoscopy, hand-assisted laparoscopy, to the most recent robotic technique.^[19] According to the International “Louisville Statement” regarding laparoscopic liver surgery published in 2009, 20%-80% of the total volume of liver surgery performed at a particular center is carried out laparoscopically.^[33] In the population-based analysis utilizing data from the Nationwide Inpatient Sample (NIS, 2000-2012) and the National Surgical Quality Improvement Project (NSQIP, 2005-2012) by Pawlik et al, the annual volume of laparoscopic liver resection has increased from 52-63 cases annually between 2000-2008 to 127-168 cases annually between 2009-2012 representing 2.4-2.7 folds increase since the release of the “Louisville Statement” in 2009.^[34] Minimally invasive liver surgery carries the advantages of a better cosmetic outcome, faster recovery, less postoperative pain and less operative blood loss and transfusion compared to the open approach without compromising morbidity or mortality.^{[34, 35]} Of note that laparoscopic repeat hepatectomy was associated with less blood loss and lower rates of transfusion in patients who had undergone previous laparoscopic surgery compared to patients who had undergone previous open surgery.^[36] Current literature has shown a learning curve for laparoscopic liver resection ranging between 45 to 75 cases.^[37] The risk-adjusted cumulative sum analysis by van der Poel et al suggested a learning curve of 55 laparoscopic hemihepatectomies.^[38] The largest review of laparoscopic liver resection in 2804 patients by Nguyen et al shows that the most common laparoscopic liver resection was wedge resection (45%) followed by laparoscopic liver segmentectomy (20%), right hepatectomy (9%) and left hepatectomy (7%).^[39] The conversion rate within the same study cohort from laparoscopic to open laparotomy and from laparoscopic to hand-assisted approach was 4.1% and 0.7% respectively with no reported intraoperative death.^[39] For cancer patients, negative resection margins were achieved in 82%-100% associated in patients with hepatocellular carcinoma with overall and disease-free survival rates of 50%-75% and 31%-38.2% respectively.^[39] The “Louisville Statement” recommended the utilization of laparoscopic liver resection for solitary lesions, 5 cm or less, located in the peripheral liver segments 2 to 6.^[33] Larger tumors (>5 cm), central, multiple, bilateral or anatomically in contact with the liver hilum, major hepatic veins or the IVC are not recommended for laparoscopic resection although they might be part of the everyday practice of highly experienced centers.^[33] The matched comparison between robotic versus laparoscopic hepatectomy by Tsung et al displayed no significant difference regarding operative and postoperative outcome measured by operative blood loss, transfusion rate, resection margin status, length of hospital stay, or 90-day mortality.^[40] Patients undergoing robotic liver surgery have longer operative time compared to the laparoscopic approach (253 min vs 199 min, however the robotic approach allowed for completion of major hepatectomies in a purely minimally invasive fashion in 81% of the cases compared to 7.1% of the cases performed laparoscopically (P<0.05).^[40]

 

 

Minimizing blood loss during liver surgery is a variable associated with favorable outcomes regarding both morbidity and mortality.^{[41, 42]} For this reason, wise utilization of various intraoperative techniques for hemodynamic control is essential for better operative outcomes. Two main methods for inflow control to the liver to be resected are available. Extrahepatic dissection of the portal pedicle with ligation and division of the arterial and venous inflow is the standard technique utilized for hepatic resection. An alternative technique is the use of mass ligation of the pedicle to the corresponding segment or segments of the liver.^[43] This latter technique provides for more rapid inflow control and allows the surgeon to avoid the risk of injury to the contralateral pedicle to the FLR, but is limited in its application to patients whose tumors are not in proximity to the inflow and who have conventional venous and arterial anatomy.

 

 

Although complete liver mobilization is traditionally an early step in hepatic resection, the position and size of some tumors make safe mobilization of the liver difficult (e.g. large bulky right-sided tumors that involve the diaphragm). Concern for the risk of tumor rupture during mobilization as well as the general principle of use of a “no-touch” technique in oncologic surgery prompted the introduction of the anterior approach. Described by Lai and colleges in 1996,^[44] this concept is considered one of the major recent advances in the field of liver resection. In 2001 the LHM was introduced by Belghiti and colleagues to allow for a better control of the transection plane during the anterior approach.^[45] This technique requires lifting the liver with a tape passed between the anterior surface of the IVC and the liver parenchyma so as to define the transection plane and better control the vasculature during transaction.^[45] Further, it allows improvement in hemodynamic stability and provides better protection of IVC from accidental injuries.

 

The so-called “ALPPS” procedure is a 2-phase procedure that was first described by Schnitzbauer and colleges in 2012.^[46] This procedure was designed to be used as an alternative to PVE in patients with marginally resectable tumors with an inadequate size FLR.

 

This phase starts with real-time evaluation using IOUS for precise assessment of tumor extent across liver lobes. Following this step, resection of the tumor from the FLR is performed along with ligation of the portal veins feeding the remaining diseased liver. A parenchymal transection is then performed between the FLR and the diseased liver. This step is necessary to ensure no collateral portal flow takes place between the FLR and the diseased liver compromising the intended surgical anatomical isolation between both.

 

As a result of the above-described procedure, the patient is left with an “auxiliary” liver that has hepatic arterial inflow, venous outflow,and biliary drainage, despite being “de-portalized”. This helps to minimize the chance of potential liver failure during the 1-2 weeks before the second stage of the operation. Further, there is rapid hypertrophy of the FLR during the window between the 2 phases of the operation allowing for median volume increase of 74% (range 21%-192%) during a median waiting period of 9 days (range 5-28).^[46]

 

This phase is performed 1-2 weeks after Phase I and entails removal of the diseased part of the liver using simple transection of the hepatic artery, duct and veins leaving the healthy and newly hypertrophied FLR to support the patient.

Since the initial introduction of the ALPPS technique, there have been several modifications suggested by other authors and a fair amount of controversy over its specific applications in the field of hepatic surgery including the concerns about the effect of ALPPS on tumor proliferation.^[47-49]

 

For unresectable liver tumors, isolated liver perfusion is a novel and alternative option in some cases.^[50] The technology aims to isolate the liver from the systemic circulation and connects it into another external mechanical perfusion system. Heated chemotherapy is then infused through this system into the hepatic vasculature. This technique helps selectively deliver chemotherapy only to the liver which allows drug delivery at higher concentrations than can be tolerated through the systemic infusion. The heated chemotherapy increases the susceptibility of malignant liver cells towards the toxic effect of chemotherapy through by enhancing its absorption. This eliminates most of the systemic side effects associated with delivering chemotherapy through systemic infusion. Many groups have reported survival benefit from this technique, but still more data are needed to establish the role of this technology in the treatment of hepatic malignancies.^[51]

 

Ex vivo resection is a novel surgical technique that has been introduced to the field of liver surgery by Pichlmayr and colleagues.^[52] This technique was developed to address liver tumors that are not resectable due to an involvement of the major vascular components including the IVC, superior vena cava, and major hepatic veins. Four crucial steps constitute the backbone of this operation: veno-venous bypass, perfusion of the liver with preservation solution under hypothermic conditions, resection of the hepatic tumor with vascular reconstruction and reimplantation of the remnant liver.^[53] Although this technique is associated with less blood loss compared to in vivo resection, the operation time is much longer, and there is some risk of hepatic injury from the period of cold preservation to the future liver remnant. Compared to total vascular exclusion, ex vivo resection was associated with better tolerance to ischemia represented as better postoperative hepatic and renal function, as well as less postoperative morbidity.^[54]

 

 

Considering the clinicopathological nature of hepatic lesions, the comprehensive assessment and proper choice of the liver resection technique in highly selected patients is associated with improved surgical oncological outcome. Patients with underlying marginal future liver remnant volumes can now safely benefit from a wider range of surgical intervention, a breakthrough that significantly improved morbidity and mortality in this group of patients.

 

 

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