Malignant Liver Tumors: Current and Emerging Therapies

By Pierre-Alain Clavien

This comprehensive and critical review of current and established treatment modalities for malignant liver tumors is designed to help you sort through the proliferation of competitive approaches and choose the best treatment options for your patient. Dr. Clavien and his contributors consider all the options – radiological, surgical, pharmaceutical, and emerging/novel therapies – and help you find the best single or combined therapy.

Building on the success of the previous edition, this extremely thorough revision:

• features a new section on Guidelines for Liver Tumors, where you will find specific strategies for treating common liver malignancies; the guidelines were prepared by the Associate Editors and take into account national and international society guidelines
• reflects actual practice by taking a multidisciplinary approach, with contributions from international experts who have extensive experience with this patient population
• achieves comprehensive and balanced coverage by having each chapter reviewed by the Editor, Deputy Editor, two Associate Editors, and at least one external reviewer
• includes 16 new chapters that cover liver anatomy, histologic changes in the liver, epidemiology and natural history of HCC, CCC and colorectal liver metastases, strategies of liver resection, and economic aspects as well as novel therapies
• facilitates the kind of daily interaction among hepatologists, hepatic surgeons, medical oncologists, radiotherapists, and interventional radiologists that is essential when treating patients with complex liver malignancies

In 44 chapters organized into six major sections, the book covers the full range of liver tumors. The perfect blend of evidence and experience, Malignant Liver Tumors: Current and Emerging Therapies, 3rd Edition, illuminates the path to better patient care.

• Language: English
• Publisher: Wiley
• Release date: Sep 23, 2011
• ISBN: 9781444356397

Book preview

1

Introduction

1

From Promethean to Modern Times

Kuno Lehmann, Stefan Breitenstein, and Pierre-Alain Clavien

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland

From myths to mysteries

In the dark ages of our ancestors, liver surgery was inexistent and the organ was a source for myths, legends, and spirituality. During the Babylonian era (~3000–1500 BC), the liver was thought to bear the soul. Priests used hepatos-copy in animal livers as a tool for divine connection, predicting the future. Clay models of sheep livers, probably used for teaching or divination, still exist from this period.

The famous legend of Prometheus was written by Hesiod (750–700 BC), recounting very ancient times (Figure 1.1). Prometheus stole fire from Zeus, the godfather of ancient Greece, and gave it to mankind. For this infringement, the angry Zeus chained him to a rock and sent an eagle to devour his liver. Prometheus was captured in eternal pain. The liver regenerated and gained its normal size overnight, and the hungry eagle returned daily to its victim. Over 2000 years later, the amazing regenerative capacity of the liver is no longer a mystical tale, but the basis for current hepato-biliary surgery and a promising topic of surgical research [1].

Probably the first anatomist to describe the liver was the Alexandrian Herophilus (330–280 BC). Although his written work has not survived, another famous scientist cited him. This was the Greek Galen (130–200 AD), who dominated medical literature for the following centuries. He made accurate descriptions of the lobar anatomy and the vasculature, interpreting the liver as the source of blood. In contrast to his empirical anatomic insights, he propagated a humoral basis of medicine. Originating from the theories of Hippocrates (460–380 BC), diseases were based on an imbalance of the four humors: black and yellow bile, blood and phlegm. However, in the following years and centuries of the Middle Ages, theories became traditions and knowledge moved forward very little. Brilliant exceptions were Leonardo da Vinci’s drawings of the extra-and intra-hepatic portal and venous vessels.

In 1640, Johannis Walaeus, from Leiden, Netherlands, reported a common tunic, surrounding the branches of the choledochal duct, the celiac artery, and the portal vein. In 1654, Francis Glisson, from Cambridge, England removed the liver parenchyma by cooking the organ in hot water and explored the hepatic blood flow with colored milk [2]. He discussed the intrahepatic anatomy and topography of the vasculature (Figure 1.2). The growing knowledge of liver anatomy was one of the substantial preconditions for the development of liver surgery. However, this was still far from realization, and the liver remained a fragile bleeding mystery. We would like to refer to the comprehensive overview by McClusky et al for the fruitful interaction between anatomists and pioneers of liver surgery [3].

Of inquisitive anatomists and courageous surgeons

In 1842, Crawford W. Long used ether as a surgical anesthetic for the first time in the United States. This was a fundamental step in the development of abdominal surgery. In 1867, Joseph Lister from Glasgow, Scotland, introduced antiseptic techniques against bacterial infections after Louis Pasteur, from Paris, France, had discovered the dangers of bacteria.

Before this period, only anecdotal records exist of descriptions about the removal of protruding liver tissue after trauma. Among these surgeons were Ambroise Paré from Paris, France, J.C. Massie from the United States, Victor von Bruns from Germany, and many others. However, liver trauma at this time was generally managed without operation. It took many years before any courageous surgeon was successful in the first attempt of a planned liver resection.

Carl Langenbuch from Berlin, Germany (Figure 1.3), who was among those to perform the first cholecystectomy, reported the first elective and successful hepatic resection in 1888 [4]. William W. Keen from Philadelphia performed the first liver resection in the United States in 1891. He used the finger-fracture technique to divide the liver parenchyma. By 1899, the first case series were being reported in the United States [5]. The most striking challenge at this time was the control of intraoperative bleeding. In 1896, Michel Kousnetzoff and Jules Pensky introduced a continuous mattress suture above the resection line for bleeding control [6]. In 1908, J. Hogarth Pringle from Glasgow, Scotland described a method of temporary compression of the portal ligament in a small series of patients [7]. However, it took 70 years before tolerance of this maneuver – exceeding 20 min – was shown [8].

Figure 1.1 Prometheus bound to a rock, with an eagle eating out his liver. 550 BC.

Figure 1.2 I ntrahepatic vasculature as illustrated in Francis Glisson’s Anatomia Hepatis (1654). (Reproduced from Glisson [2], with permission.)

Figure 1.3 Carl Langenbuch (1846–81).

Bleeding control remained a major limiting factor in the development of hepatic surgery for many years. The fine work of anatomists provided the key insights to overcome major bleeding. In 1888, Hugo Rex from Germany [9], and in 1897 James Cantlie from Liverpool, England [10], revisited the accepted anatomic division of the liver by the falciform ligament. Using corrosion studies, they separated the liver by the branches of the portal vein and defined an avas-cular plane through the gallbladder bed. Today, the plane passing through the gallbladder bed towards the vena cava and through the right axis of the caudate lobe along the middle hepatic vein is known as the Rex–Cantlie line. Walter Wendell from Magdeburg, Germany [11] and Hans von Haberer from Graz, Austria [12] were the first surgeons at the beginning of the 20th century to apply resections along this anatomic plane.

Following World War II, Carl-Herman Hjortsjo from Lund, Sweden [13] and John E. Healey from Huston, United States [14] further refined hepatic anatomy by their description of the intrahepatic biliary duct system and the vascular tree. In 1954, Claude Couinaud from Paris, France (Figure 1.4) published his seminal work on the segmental architecture of the liver [15, 16]. Based on the branches of the portal vein, he separated the liver into eight well-described segments. Before this time, liver resections were mostly performed in a blindly manner. The findings of Carl-Herman Hjortsjo, John Healey, and Claude Couinaud had a major impact on surgical technique and related mortality. The rapidly evolving era of liver surgery had begun.

In 1950, Ichio Honjo from Kyoto, Japan reported the first anatomic liver resection [17]. Jean-Louis Lortat-Jacob from Paris, France in 1952 [18], followed by Julian. K. Quattlebaum, from Georgia, United States in 1953 [19], reported the first resections in Europe and the United States. Subsequent, descriptions of the procedure were provided by Alexander Brunschwig [20] and George T. Pack [21] in New York, United States, and later by William P. Longmire and Samuel A. Marable [22] in Los Angeles, United States.

At this time, George T. Pack documented the regenerative potential of the human liver after a major hepatectomy [23]. A few years later, Tien-Yu Lin and Chiu-Chiang Chen from Taipei, Taiwan described the decrease of regenerative capacity of the cirrhotic liver [24]. The knowledge about liver regeneration in humans was preceded by animal experiments years before. In 1879, Hermann Tillmanns from Leipzig, Germany [25] demonstrated regeneration in rabbit livers. In 1883, Themisocles Gluck from Berlin [26], and later Emil Ponfick from Breslau, Germany, demonstrated liver regeneration after major resections in animals.

In the 1960s, perioperative mortality rates up to 50% were common after right hemihepatectomy. Furthermore, serious concern was growing over hepatic nomenclature, and notably, liver surgeons throughout the world used different, sometimes confusing, terms [27]. In 2000, a group of international liver surgeons proposed a standardized nomenclature, which was introduced at the bi-annual meeting of the International Hepato-Pancreato-Biliary Association (IHPBA) in Brisbane, Australia. The terminology for hepatic anatomy was subsequently called the Brisbane nomenclature [28]. Nomenclature in hepatic surgery is discussed in detail in Chapter 2.

Figure 1.4 Claude Couinaud working with his collection of liver casts at the School of Medicine in Paris, 1988.

Over the years, growing anatomic and physiologic knowledge, and ongoing specialization in experienced centers, have significantly lowered mortality from liver resections to below 5% [29]. We would like to refer to the comprehensive overviews by Joseph G. Fortner and Leslie H. Blumgart [30], and James H. Foster [31], for an in-depth coverage of liver surgery in the 20th century.

The era of liver transplantation

A giant leap forward and a driving force in the rapid development of hepatobiliary surgery was the onset of the transplantation era. In 1955, Cristopher S. Welch from Albany, United States, published the first heterotopic liver transplantation in a dog [32]. Others, such as J. A. Cannon, Thomas E. Starzl, and Francis D. Moore, followed with orthotopic liver transplantations (OLT), also in dogs, and established the basis for transplantation in humans [33]. In 1963, Thomas E. Starzl (Figure 1.5) made the first attempt to transplant a human liver in Denver, United States [34]. However, the patient died during the operation. Another attempt by Francis D. Moore in Boston also did not succeed [35]. The first series of successful OLTs was reported in 1968 by Thomas E. Starzl [36].

Figure 1.5 Thomas E. Starzl has the honor of the first pitch at the Three Rivers Stadium in 1983, Pittsburgh. (Reproduced from the Pittsburgh Post-Gazette.)

A year later, Sir Roy Calne performed the first OLT in Europe in Cambridge, England [37]. However, although many patients initially tolerated the transplantation well, most did not survive OLT longer than a few weeks or months.

Another quantum leap was the discovery of cyclosporine A (CyA) by Hartmann F. Stahelin and Jean-Francois Borel from Basel, Switzerland, in 1972. Seven years later, Sir Roy Calne reported the first use of CyA in OLT patients with a dramatic improvement in long-term survival [38]. Before the introduction of CyA, 5-year survival after OLT was less than 20% and improved to 60% or more with the introduction of CyA [39]. In the late 1980s, Thomas E. Starzl introduced FK-506 (tacrolimus) as a new and promising immunosuppressant at the University of Pittsburgh. The introduction of effective immunosuppressants such as poly-clonal antilymphocyte antibodies, anti-CD3 antibodies in the 1980s, or mycophenolate mofetil (MMF) in the early 1990s, and rapamycin in the late 1990s offered further alternatives in the management of patients after OLT.

Already in the early stage of solid organ transplantation, it was recognized, that success could only be achieved with adequate preservation of the organs. Cold preservation was described as early as 1912 by the French surgeon Alexis Carell, who preserved and transplanted vessels, skin, and connective tissues in dogs [40]. Together with the famous aviator and engineer Charles A. Lindberg, he constructed a perfusion pump and successfully preserved thyroid glands [41]. Years later, in the era of liver transplantation, the relevance of cooling the donor organ was recovered during animal experiments by Francis D. Moore [33]. Lawrence Brettschneider from Denver, United States used cooling of the animal donor organ and intraportal infusion with a balanced, cooled electrolyte solution, buffered to pH. The organ was additionally perfused after harvesting, but this technique was much too complex for clinical application [42]. For many years, storage in cold Collins solution was the standard for organ procurement [43]. A landmark advance was the development of the University of Wisconsin (UW) solution by Folkert O. Belzer and James H. Southard in 1988 [44], representing an important growth of knowledge in the pathophysiology of ischemia/reperfusion injury. This solution contains colloids to prevent cell swelling, the oxygen scavengers allopurinol and glutathione, and adenosine to facilitate adenosine triphosphate (ATP) production.

In 1983, a National Institutes of Health (NIH) Consensus Conference considered liver transplantation as an accepted therapy for patients with end-stage liver disease. The consequence of this statement was a rapid increase in the numbers of patients on waiting lists in the following years, resulting in a dramatic shortage of available donor organs for transplantation. The development of new concepts was therefore crucial.

Figure 1.6 Henri Bismuth.

The shortage of size-matched liver donors for pediatric patients was responsible for a high death rate on the cadaveric pediatric waiting list. This stimulated the development of technical innovations based on the segmental anatomy of the liver. Reduced liver graft, split graft, and living donor liver transplantation were such innovative techniques. In 1984, Henri Bismuth (Figure 1.6) from Paris, France, performed the first OLT using a left hemiliver [45]. In 1988, Rudolf Pichlmayr from Hannover, Germany extended the concept of partial liver graft transplantation and published in 1988 a report of a split graft, where the right hemiliver was transplanted to an adult, and the left to a child [46]. Two years later, Christoph E. Broelsch published the first patient series of split liver transplantation in Chicago, United States [47]. The introduction of living donors was a critical step in the further evolution of liver transplantation [48]. In 1989, Silvano Raia from Sao Paulo, Brazil [49], and one year later Russell W. Strong from Brisbane, Australia [50], reported the first living donor liver transplantations using the left hemiliver. In 1994, Yoshio Yamaoka from Kyoto, Japan used the right hemiliver for transplantation, expanding this procedure also for adults [51]. The first series of patients was published by Christoph E. Broelsch in Chicago [52], later by Chung-Mau Lo in Hong Kong [53].

Nowadays, patient survival after one year has reached 80–90% in many contemporary series of OLT [54]. Consequently, donor criteria are still expanding under the pressure of an insufficient donor pool. Beside end-stage liver disease and acute liver failure, selected patients with primary liver cancer [55] and early stage hilar cholangiocarcinoma [56] have become accepted indications for OLT (see also Chapter 26 for indications of OLT in treatment of liver tumors).

A potential approach to solve the shortage of donor organs was the use of steatotic donor organs and this was shown to have a favorable outcome by McCormack et al [57]. Donor risk scores and appropriate matching to selected recipients may further improve the outcome [58]. Thus, extending donor criteria, improvement of allocation procedures, and finally, translation of knowledge from basic research about donor organ protection into clinical application, may help to overcome the problem of donor organ shortage in the near future.

Surgical oncology: breaking down the limits

Parallel to the progress in the field of liver transplantation, liver surgery, mostly for oncologic diseases, became more sophisticated. In 1983, William P. Longmire from Los Angeles, California, published the results of 138 patients after major resections with a 30-day mortality of 10% [59]. In the 1990s, Jacques Belghiti from Paris, France reported – in a large series of 747 patients – a mortality of 1% in patients with normal liver parenchyma [60]. Leslie H. Blumgart from New York, United States [61] and Sheung Tat Fan from Hong Kong [62] published similar results. However, the presence of cirrhosis [63], portal hypertension [64], and liver steatosis [65] were identified as important risk factors for perioperative morbidity and mortality.

An important step for the improved outcomes was the understanding that these complex diseases must be treated in specialized, interdisciplinary centers [66]. A higher caseload in such hepato-pancreatico-biliary (HPB) centers translates into more experience, an important factor for favorable outcomes [67, 68].

In the last decades, basic research provided new insights into liver physiology and pathophysiology [69–71]. Inter-leukin-6 [72], tumor necrosis factor a [73], platelet-derived serotonin [74], and bile salts [75] were identified as central mediators of liver regeneration. Explorations of mechanisms of ischemic damage and cell death provided novel perceptions of liver injury [76–79]. However, only few new strategies, such as ischemic preconditioning, made the transition into clinical practice [80].

Diagnostic accuracy improved due to the availability of computed tomography (CT) scans and magnetic resonance (MR) tomography. Masatoshi Makuuchi, from Tokyo, Japan, introduced the concept of routine intraoperative ultrasonography for liver surgery [81]. He was also among the first to use portal vein embolization to increase the future liver remnant prior to major resection [82], although the mechanism of selective portal occlusion and subsequent contralateral hypertrophy was already known since 1920 [83]. For the treatment of unresectable tumors, radiofrequency was introduced as an alternative treatment [84–86].

The complex treatment strategies for metastatic liver disease are illustrative examples of the progress of HPB surgery [1]. In 1940, Richard B. Cattell, in Boston, United States, performed the first resection of a metastatic tumor [87], although resection of colorectal liver metastases remained controversial until the early 1980s. The survival of patients after resection was 21%, but the operative mortality still reached 17% [88]. Today, resection for liver metastasis, especially of colorectal origin, provides favorable outcomes compared to the natural history [89]. In a series of 1001 consecutive patients, the 5-year survival rate was 37% [1, 90]. In selected patients with unresectable and multifocal metastases, a two-stage hepatectomy combined with chemotherapy was recognized as an effective and safe treatment strategy [91]. In 2004, promising survival rates for patients treated with two-stage procedures, combined with portal vein ligation, were published [92]. Down-staging of previously unresectable colorectal liver metastases could also be achieved by portal vein ligation combined with intra-arterial chemotherapy [93]. Multistage procedures are currently recognized as effective strategies for patients with otherwise unresectable tumors [1].

In conclusion, liver surgery has enjoyed a dramatic development during the last three decades. Surgical experience and outcomes after major surgery improved as a result of progress in many fields. Furthermore, multidisciplinary patient management became a mainstay of care in recognized HPB centers. Today, liver surgery no longer carries the high risk that it did in its infancy. In experienced hands, liver surgery became reliable and effective, and consequently saved the lives of many patients.

Self-assessment questions

1 Name the surgeon who performed the first successful liver resection.

2 Name the surgeons who performed the first major liver resections.

3 What was a prerequisite for safe major liver surgery?

4 What was the major innovation making OLT a successful treatment?

5 A great problem was the availability of size-matched donor organs for children. Who found the solution, which had also a major impact on later developments?

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Self-assessment answers

1 Carl Langenbuch, a German surgeon, performed the first successful liver resection in 1888 in Berlin.

2 Ichio Honjo reported the first anatomic liver resection in 1950 in Kyoto, Japan. In 1952, Jean-Louis Lortat-Jacob from Paris, France reported the first resection in Europe, followed by Julian K. Quattlebaum from Georgia, who reported the first resections in the United States in 1953.

3 The fine work of Carl-Herman Hjortsjo from Lund, Sweden, John E. Healey from Huston, United States and Claude Couinaud from Paris, France revealed the complex anatomy of intrahepatic structures, a fundamental basis for safe liver surgery.

4 Before the advent of cyclosporine A, discovered in 1972 by Hartmann F. Stähelin and Jean-Francois Borel from Basel, Switzerland, the prognosis after OLT was poor. Cyclosporine A improved the outcome of these patients significantly.

5 The segmental anatomy of the liver was the key to the problem. Henri Bismuth from Paris, France performed the first OLT using a left hemiliver in 1984. Later, Rudolf Pichlmayr from Hannover, Germany performed a split graft, where the right hemiliver was transplanted to an adult, and the left to a child. This principle was also the basis for living related liver transplantation.

2

Hepatic Anatomy and Terminology

Steven M. Strasberg

Section of Hepatobifiary-Pancreatic Surgery, Washington University in Saint Louis, Saint Louis, MO, USA

Overview

A clear understanding of hepatic anatomy is critical to the planning and conduct of liver surgery. The branching pattern of the hepatic artery and bile ducts within the liver is regular and virtually identical to each other, unlike for the portal vein. Consequently the Brisbane 2000 Terminology of Hepatic Anatomy and Resections of the International Hepatobiliary Pancreatic Association (IHBPA) [1] (Members of the Committee of the Brisbane Classification: Strasberg SM, Belghiti J, Clavien PA, Gadzijev E, Garden JO, Lau W, Maku-uchi M, Strong RW) is based on the anatomy of the hepatic artery and bile duct. The IHBPA terminology has now been adopted by most major textbooks of hepatic anatomy and surgery. In this chapter the most common anatomic pattern is referred to as the prevailing pattern. All other patterns are anomalies and they need not be rare.

Anatomic basis of the Brisbane 2000 Terminology: Division of the liver based on the hepatic artery and bile ducts

The primary (first-order) division of the proper hepatic artery is into the right and left hepatic arteries (Figure 2.1). These branches supply arterial blood to the right and left hemilivers or livers (Figure 2.2). The plane between two distinct zones of vascular supply is called a watershed. The watershed of the first-order division intersects the gallbladder fossa and the fossa for the inferior vena cava (Figure 2.2). It is called the mid-plane of the liver.

The second-order division (Figures 2.1 and 2.3) of the hepatic artery is into four sectional arteries, two on the right and two on the left (Figure 2.1). On the right side, the right anterior sectional artery and the right posterior sectional hepatic artery supply arterial blood to the right anterior section and the right posterior section (Figure 2.3). The plane between these sections is the right intersectional plane, which does not have any markings on the surface of the liver to indicate its position. On the left, the left medial sectional hepatic artery and a left lateral sectional hepatic artery (Figure 2.1) supply arterial blood to the left medial section and the left lateral section (Figure 2.3). The plane between these sections is the left intersectional plane, which does have surface markings indicating its position. These are the umbilical fissure and the line of attachment of the falciform ligament to the anterior surface of the liver.

The third-order division of the hepatic artery is into seg-mental arteries (Figure 2.1) and divides the liver into seven segments (segments (Sg) 2–8) (Figures 2.1 and 2.4). Each of the segments has its own feeding segmental artery. The left lateral section is divided into Sg 2 and Sg 3. The pattern of ramification of vessels within the left medial section does not permit subdivision of this section into segments, each with its own arterial blood supply. Therefore, the right medial section and Sg 4 are synonymous. However, Sg 4 is arbitrarily divided into superior (4a) and inferior (4b) parts without an exact anatomic plane of separation based on internal ramification of vessels. Note then that Sg 4 and the right medial section are identical. The right anterior section is divided into two segments, Sg 5 and Sg 8. The right posterior section is divided into Sg 6 and Sg 7. The planes between segments are referred to as intersegmental planes. The ramification of the bile ducts is identical to that described for the arteries and the zones of the liver drained by the ducts are identical to the zones supplied by the respective arteries.

Sg 1 (caudate lobe) is a distinct portion of the liver, separate from the right and left hemilivers (Figure 2.5). It consists of three parts, the bulbous left part (Spiegelian lobe), hugging the left side of the vena cava and readily visible through the lesser omentum; the paracaval portion, anterior to the vena cava; and the caudate process, on the right, merging indistinctly with the right hemiliver. It lies posterior to the hilum and the portal veins and its upper extent is limited by the hepatic veins, which lie anterior and superior to the paracaval portion of the caudate lobe [2, 3] (Figure 2.5). It receives vascular supply from both right and left hepatic arteries (and portal veins). Caudate bile ducts drain into both right and left hepatic ducts [2, 3]. The caudate lobe is drained by several short caudate veins that enter the inferior vena cava (IVC) directly from the caudate lobe. Their number and size is variable. On occasion caudate veins are quite short and wide, and therefore must be isolated and divided cautiously. Commonly, these veins enter the IVC on either side of the midplane of the vessel, an anatomic feature which normally allows passage of a clamp behind the liver on the surface of the IVC without encountering the caudate veins.

Figure 2.1 Prevailing pattern of branching of the hepatic artery. The proper hepatic divides into the right (A) and left (B) hepatic arteries, which supply the right and left hemilivers (see Figure 2.2) respectively. The right hepatic artery divides into anterior (c) and posterior (d) sectional arteries, which supply the right anterior and right posterior sections (see Figure 2.3). The right anterior sectional artery divides into two segmental arteries, which supply Sg 5 and Sg 8 (see Figure 2.4) and the right posterior sectional artery divides into arteries that supply Sg 6 and Sg 7. The left hepatic artery (B) also divides into two sectional arteries, the left medial (e) and left lateral (f). The former supplies the left medial section (see Figure 2.3) also called Sg 4, while the latter supplies the left lateral section. The left lateral sectional artery divides into segmental arteries to Sg 2 and Sg 3 (see Figure 2.4). The caudate lobe (Sg 1 and Sg 9) are supplied by branches from A and B. Bile duct anatomy and nomenclature are similar to those of the hepatic artery. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Figure 2.2 Nomenclature for first-order division anatomy (hemilivers) and resections. The border or watershed of the first-order division which separates the two hemilivers is a plane which intersects the gallbladder fossa and the fossa for the inferior vena cava (IVC) and is called the midplane of the liver. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Terminology of liver resections

Terminology of resections is based upon anatomic terminology. Resection of one side of the liver is called a hepatectomy or hemihepatectomy (Figure 2.2). Resection of the right side of the liver is a right hepatectomy or hemihepatectomy, and resection of the left side of the liver is a left hemihepatec-tomy or hepatectomy. Resection of a liver section is referred to as a sectionectomy (Figure 2.3). Resection of the liver to the left side of the umbilical fissure is referred to as a left lateral sectionectomy. The other sectionectomies are named accordingly: left medial sectionectomy, right anterior sectionec-tomy, and right posterior sectionectomy. Resection of three contiguous sections is referred to as a trisectionectomy. When the sections are right posterior section, right anterior section, and right medial section (right liver plus Sg 4), this is referred to as a right trisectionectomy (Figure 2.3). Similarly, resection of the two sections of the left hemiliver plus the right anterior section is referred to as a left trisectionectomy (Figure 2.3).

Resection of one of the numbered segments is referred to as a segmentectomy (Figure 2.4). Resection of the caudate lobe can be referred to as a caudate lobectomy or resection of Sg 1. It is always appropriate to refer to a resection by the numbered segments. For instance, it would be appropriate to call a left lateral sectionectomy a resection of Sg 2 and Sg 3.

Figure 2.3 Nomenclature for (a) second-order division anatomy (sections, based on bile ducts and hepatic artery) and (b) other sectional liver resections, including extended resections. The borders or watersheds of the sections are planes referred to as the right and left intersectional planes. The left intersectional plane passes through the umbilical fissure and the attachment of the falciform ligament. There is no surface marking on the right intersectional plane. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Surgical anatomy for liver resections

Hepatic arteries

In the prevailing anatomic pattern, the celiac artery terminates by dividing into common hepatic and splenic arteries. Rarely the hepatic artery arises directly from the aorta (Figure 2.6). The common hepatic artery runs for 2–3 cm anteriorly and to the right to ramify into gastroduodenal and proper hepatic arteries. The proper hepatic artery enters the hepatoduodenal ligament, normally runs for 2–3 cm along the left side of the common bile duct, and terminates by dividing into the right and left hepatic arteries, the right artery immediately passing behind the common hepatic duct. The four sectional arteries arise from the right and left arteries 1–2 cm from the liver. The preceding description is the prevailing pattern but variations are very common (Figure 2.7). The surgeon is wise not to make assumptions regarding hepatic arteries based on size or position, but to rely instead on exposure, trial occlusions, and radiologic support.

Replaced arteries are surgically important anomalies. Replaced means that the artery supplying a particular part of the liver is in an unusual location and also that it provides the sole blood supply to that part of the liver. Aberrant means the structure is in an unusual location. While the definition of aberrant does not state whether the structure provides sole supply, it is usually considered to be synonymous with replaced in respect to these arteries. Accessory refers to an artery which is additional, i.e. is present in addition to the normal structure and as a result is not the sole supply to a volume. Consequently, ligation of an accessory artery does not cause ischemia.

Figure 2.4 Nomenclature for third-order division anatomy (segments) and resections. The borders or watersheds of the segments are planes referred to as intersegmental planes. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Figure 2.5 Schematic representation of the anatomy of the caudate lobe. The caudate lobe consists of three parts, the caudate process (CP) on the right, the paracaval portion anterior to the vena cava (PC), and the bulbous left part (Spiegelian lobe, SL). IVC, inferior vena cava; PV, portal vein; RHV, MHV, LHV, right hepatic, middle hepatic and left hepatic veins, respectively; RPV, LPV, left and right portal vein, respectively (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Figure 2.6 CT scan of patient with absent celiac artery. Hepatic artery (HA), splenic artery (SA) (labeled b in sagittal view, inset) and left gastric artery (labeled a in sagittal view, inset) arise independently from the aorta. Superior mesenteric artery is labeled c in inset. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Approximately 25% of patients have a replaced hepatic artery. A replaced right hepatic artery arises from the superior mesenteric artery and runs from left-to-right behind the lower end of the common bile duct to emerge and course on its right posterior border. It may supply a segment, section, or the entire right hemiliver. Rarely its supplies the whole liver and then it is called a replaced hepatic artery. A replaced left hepatic artery arises from the left gastric artery and courses in the lesser omentum with vagal branches to the liver. It may also supply a segment, section, hemiliver, or very rarely the whole liver. Sometimes left hepatic arteries arising from the left gastric artery are actually accessory, and exist in conjunction with normally situated left hepatic arteries. Replaced arteries may confer an advantage during surgery. For instance, when a replaced left artery supplies the left lateral section, it is possible to resect the entire proper hepatic artery when performing a right trisectionec-tomy for hilar cholangiocarcinoma.

In performing hepatectomies by the standard technique of isolating individual structures instead of pedicles, it is necessary to correctly identify the particular artery(ies) supplying the volume of liver to be resected. A helpful rule is that an artery located to the right side of the bile duct always supplies the right side of the liver, but arteries found on the left side of the bile duct may supply either side of the liver. Therefore, when using the individual vessel ligation method, it is important to determine the position of the common hepatic duct.

Figure 2.7 A dangerous anomaly. In this patient the right hepatic artery (RHA) came off the gastroduodenal artery (GDA). The common hepatic artery (CHA) divided into the left hepatic artery (LHA) and the GDA. There was no proper hepatic artery. The LHA could easily be mistaken for the proper hepatic artery. Ligation of the GDA could lead to arterial devascularization of the right liver. Note early branching of the RHA into anterior and posterior sectional branches. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Bile ducts

Prevailing pattern and variations of bile ducts draining the right hemiliver

Normally the right hepatic duct is a short structure with only about 1 cm in an extrahepatic position. The prevailing pattern of bile duct drainage is shown in Figure 2.8a. The segmental ducts from Sg 6 and Sg 7 (called B6 and B7) unite to form the right posterior sectional bile duct and the segmental ducts from Sg 5 and Sg 8 (B5 and B8) unite to form the right anterior sectional bile duct (Figure 2.8a). The sectional ducts unite to form the right hepatic duct, which unites with the left hepatic duct at the confluence to form the common hepatic duct.

There are two important sets of biliary anomalies on the right side of the liver. In the first, a right sectional bile duct joins the left hepatic duct. This is a common anomaly. The right posterior sectional duct inserts into the left hepatic duct in 20% of individuals (Figure 2.8b) and the right anterior bile duct does so in 6% (Figure 2.8c). A right sectional bile duct inserting into the left hepatic duct may be injured during left hepatectomy if the left duct is divided close to the midplane of the liver (Figure 2.8b, incorrect). The left hepatic duct should be divided close to the umbilical fissure to avoid this injury (Figure 2.8b, correct). The second important anomaly is insertion of a right bile duct into the biliary tree at a lower level than the prevailing site of confluence. Low union may affect the right hepatic duct, a sectional right duct (usually the anterior one), a segmental duct, or a subsegmental duct. The duct will unite with the common hepatic duct well below the prevailing site of confluence in about 2% of individuals. In some it first unites with the cystic duct and then with the common hepatic duct.

Figure 2.8 Variations in formation of the right hepatic ducts. (a) Prevailing pattern and (b–d) some variations of bile ducts draining the right hemiliver (see text). (b,c) Separate entry of right anterior and right posterior sectional ducts (no right duct). (d) Shifting of entry of a right bile duct inferiorly. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

The right posterior sectional duct normally hooks over the origin of the right anterior sectional portal vein (Hjortsjo’s crook) [4], where it is in danger of being injured if the right anterior sectional pedicle is clamped too close to its origin (Figure 2.9).

Prevailing pattern and important variations of bile ducts draining the left hemiliver

The prevailing pattern of bile duct drainage from the left liver is shown in Figure 2.10a, and is present in only 30% of individuals, i.e. anomalous patterns are present in the majority of individuals. In the prevailing pattern the seg-mental ducts from Sg 2 and Sg 3 (B2 and B3) unite to form the left lateral sectional bile duct. This duct passes behind the umbilical portion of the portal vein and unites with the duct from Sg 4 (B4) (also called the left medial sectional duct since section and segment are synonymous for this volume of liver). The union of these ducts to form the left hepatic duct occurs about one-third of the distance between the umbilical fissure and the confluence of left and right bile ducts at the midplane of the liver. The left hepatic duct continues from this point for 2–3 cm along the base of Sg 4 to its termination. Note that it is in an extrahepatic position and that it has a much longer extrahepatic course than the right bile duct. The extrahepatic position of the left hepatic duct is a key anatomic feature, which makes this section of duct the prime site for high biliary–enteric anastomosis. The left hepatic duct runs at a variable angle. In some individuals it is almost horizontal but in others it runs sharply upward. It is much easier to expose a long length of duct in the former type.

Figure 2.9 Hjortsjo’s crook. Note that the right posterior sectional bile duct (RPSBD) crosses the origin of the right anterior sectional portal vein. RASBD, right anterior sectional bile duct. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

The major anomalies of the left ductal system involve variations in site of insertion of B4 (Figure 2.10b), multiple ducts coming from B4 (Figure 2.10c), and primary union of B3 and B4 with subsequent union of B2 (Figure 2.10d). B4 may join the left lateral sectional duct to the left or right of its point of union in the prevailing pattern (Figure 2.10b); in the former case the insertion of B4 is at the umbilical fissure, and in the latter it may occur at any place to the right of the usual point of insertion up to the site where the left lateral sectional duct unites with the right hepatic duct. Rarely the left lateral sectional duct and the duct to B4 do not unite before a confluence with the right hepatic duct. In these cases the confluence of the three ducts forms the common hepatic duct and there is no left hepatic duct.

The bile duct to Sg 3 has been used to perform biliary bypass and can be isolated by following the superior surface of the ligamentum teres to the portal pedicle for Sg 3. The technique is less commonly used now that internal endo-scopic bypass has been developed.

Prevailing pattern of bile ducts draining the caudate lobe (Sg 1)

Two to three caudate ducts normally enter the biliary tree. Their orifices are usually located posteriorly on the left duct, right duct, or right posterior sectional duct [2, 3].

Figure 2.10 Variations in formation of the left hepatic ducts. (a) Prevailing pattern and (b–d) some variations of bile ducts draining the left hemiliver. (b) Insertion of B4 shifted to right or left. (c) Multiple ducts draining B4. (d) B3, B4 form a common channel before insertion of B2. (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Portal veins

The portal vein divisions on the right side of the liver correspond exactly to those of the hepatic artery and bile duct, and they supply the same hepatic volumes. There is a right portal vein which supplies the entire right hemiliver and it divides into two sectional portal veins and four segmental portal veins (Figure 2.11) supplying the same sections and segments as the respective right hepatic arteries. On the left side of the liver, however, the left portal vein is quite unusual because of the fact that its structure was adapted to function in utero as a conduit between the umbilical vein and the ductus venosus, whereas postnatally the direction of flow is reversed. The left portal vein consists of a horizontal or transverse portion, which is located under Sg 4, and a vertical part or umbilical portion, located in the umbilical fissure (Figure 2.11). Unlike the right portal vein, neither portion of the left portal vein actually enters the liver substance, but rather lies directly on the surface. The umbilical portion is usually hidden by a bridge of tissue passing between left medial and lateral sections. This bridge of liver tissue may be as thick as 2 cm or only be a fibrous band. The junction of the transverse and umbilical portions of the left portal vein is marked by the attachment of a stout cord–the liga-mentum venosum. This structure, the remnant of the fetal ductus venosus, runs in the groove between the left lateral section and the caudate lobe, and attaches to the left hepatic vein–IVC junction.

The transverse portion of the left portal vein sends no or only a few small branches to Sg 4. Large branches from the portal vein to the left liver arise exclusively beyond the attachment of the ligamentum venosum, i.e. from the umbilical part of the vein [5]. These branches come off both sides of the vein; those arising from the right side pass into Sg 4 and those from the left supply into Sg 2 and Sg 3. There is usually only one branch to Sg 2 and one to Sg 3, but often there is more than one branch to Sg 4. The left portal vein terminates in the ligamentum teres at the free edge of the left liver. Note that the umbilical portion of the left portal vein has a unique pattern of ramification with multiple branches emanating from its sides as it narrows to terminate blindly in the ligamentum teres (Figures 2.11 and 2.12).

This unusual branching pattern of the umbilical portion of the left portal vein represents both an opportunity and a danger for the hepatic surgeon. The portal vein branches to Sg 4 may be isolated in the umbilical fissure on the right side of the umbilical portion of the left portal vein. The veins here become associated with the bile ducts and the arteries and enter Sg 4 within a segmental fibrous sheath. Isolation of these structures in this location may provide an extra tissue margin when resecting a tumor in Sg 4 that impinges upon the umbilical fissure. Also, by dividing these branches, the portal vein may be rolled to the left to allow exposure of an extra length of left lateral sectional bile ducts in operations for hilar cholangiocarcinoma. The danger of dissection in the umbilical fissure is that injury to the portal vein in this position could deprive Sg 2 and Sg 3 of portal vein supply, as well as Sg 4. It is also is possible to isolate the portal vein branches going into Sg 2 and Sg 3 in the umbilical fissure in order to extend a margin when resecting a tumor in the left lateral section. In order to access the portal vein in the umbilical fissure it is usually necessary to divide the bridge of liver tissue, between the left medial and lateral sections. This is done by passing a blunt instrument behind the bridge before dividing it, usually with cautery. Note that arteries and bile ducts passing to the left lateral section are in danger of being injured as the most posterior–superior portion of the bridge is isolated.

Figure 2.11 Ramification of the portal vein in the liver. The portal vein divides into right (A) and left (T) branches. The right portal vein divides into anterior (c) and posterior (d) sectional arteries. The branches in the right liver correspond to those of the hepatic artery and bile duct (see Figure 2.1). The branching pattern on the left is unique. The left portal vein has transverse (T) and umbilical portions (U). The transition point between the two parts is marked by the attachment of the ligamentum venosum (LV). All major branches come off the umbilical portion (see text). The vein ends blindly in the ligamentum teres (LT). (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Figure 2.12 Ramification of the left portal vein as seen on computed tomography. Note the branches to Sg 2–4 and the ligamentum teres (LT). The arrowhead points to the groove between the left lateral section and the caudate lobe. This is also the site of origin of the ligamentum venosum, where the transverse portion of the portal vein becomes the umbilical portion of the vein, proving conclusively that the branch to Sg 2 is not part of a terminal division of the transverse portion of the vein as might be concluded from cast studies. (See also ref. [5]). (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Although the anatomy of the portal vein is unusual, it is uncommon to have variations. The most common variation is absence of the right portal vein. In these cases the right posterior and right anterior sectional veins originate independently from the main portal vein; the anterior sectional vein is not readily visible because of it high position in the porta hepatis. An unsuspecting surgeon may divide the posterior sectional vein thinking that it is the right portal vein and become confused when the anterior sectional vein is come upon during hepatic transection.

Rarely there is no extrahepatic left portal vein. Failure to recognize this anomaly may lead to a catastrophic complication. The apparent right vein is really the main portal vein, a structure which enters the liver, gives off branches to the right liver, and then loops back within the liver substance to supply the left side (Figure 2.13). The vein looks like a right vein in terms of position but it is larger. Transection results in total portal vein disconnection from the liver. This anomaly should always be searched for on computed tomography (CT) scans as right hepatectomy is not usually possible when it is present. The presence of the umbilical portion of the left vein in the umbilical fissure on CT scan precludes the presence of this problem.

Figure 2.13 Absent extrahepatic left portal vein, a rare and very dangerous anomaly. Three-dimensional reconstruction of CT scan. Note that main portal vein (MPV) enters the right liver, gives off the right posterior sectional portal vein (RPSPV) and some branches to the right anterior section, and then proceeds to the left as an internal left portal vein (LPV). (Reproduced with permission from Washington University, Saint Louis, MO, USA.)

Hepatic veins and liver resection (Figure 2.14)

Normally there are three large hepatic veins. Respectively, these run in the midplane of the liver (middle hepatic vein), the right intersectional plane (right hepatic vein), and the left intersectional plane (left hepatic vein). The left hepatic vein actually begins in the intersegmental plane between Sg 2 and Sg 3, and travels in that plane for most of its length. It becomes quite a