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Principles of liver surgery
HEPATOBILIARY SURGERY
four sectors and eight segments.3 The right lobe is divided into an anterior and posterior sector by the right hepatic vein. The left lobe is divided into the medial and lateral sector by the left hepatic vein. The eight segments are numbered clockwise in a frontal plane (see Anatomy of the Liver on pp. 589e592 of this issue). Each segment is a functional, independent unit supplied by a single portal triad. The caudate lobe (segment I) is unique as it derives blood from both the right and left portal vein and hepatic artery. Couinaud’s classification of the liver provides crucial information as to the potential resection planes. Each segment functions as a self-contained unit. For the liver to remain viable, resections must proceed along the vessels that define the peripheries of the segments and therefore parallel the hepatic veins. The centrally located portal veins, bile ducts and hepatic arteries are preserved. The liver is surrounded by a fibrous capsule that was first described by Glisson in 1654.4 This fibrous capsule extends to surround the portal triads as they pass into the liver. The portal vein, hepatic artery and bile duct that run into each liver segment are surrounded by a substantial sheath.4 This is important as the fibrous sheath allows rapid control of inflow vessels to specific anatomical units within the liver and permits en masse occlusion of these vascular structures in what is known as the Pringle manoeuvre which will be discussed in more detail later.
Principles of liver surgery Natalie Peel Stephen Wigmore
Abstract In recent decades, liver resections have become safe operations for carefully selected patients. This article outlines the functional hepatic anatomy and discusses the choice of patient and operation. The principles to performing safe surgery with minimal blood loss will be addressed along with future advances.
Keywords Bleeding; embolization; hepatectomy; hepatic; liver; resection
Introduction For a variety of benign and malignant hepatic lesions, liver resection is the most appropriate treatment. The first elective liver surgery was performed in 1952 by Lortat-Jacob for the treatment of metastatic colorectal cancer, however major hepatectomies did not become standard practice until the 1980s. In recent decades, the morbidity and mortality associated with major liver resections has improved, and the indications for performing such operations have been refined making it a safe procedure in carefully selected patients. Resection of up to 75% of functional liver is now being performed in appropriate patients in several centres with a mortality that is as low as 2%.1 For those with malignant liver lesions, resection offers the best opportunity for long-term survival or cure and, for those with symptomatic benign tumours, resection is safe and effective. With the evolution of enhanced recovery programmes, the duration of hospitalization after hepatectomy is decreasing to less than 7 days in many centres with an expectation that all patients will regain normal hepatic function.
Choosing the right patient As with any major operation, preoperative assessment begins with a complete history and examination to determine the patient’s general health. Patients with risk factors should undergo detailed cardiopulmonary assessment. Antithrombotic medication such as warfarin or clopidogrel should be noted and arrangements made to stop treatment before admission to hospital. It is important to identify any underlying co-morbidities that would preclude a major liver resection. In the past, patients over the age of 70 years old were considered poor surgical candidates however several recent studies have shown that age in itself is not necessarily an obstacle to liver resection.5,6 Excision of colorectal metastasis is the most common reason for performing a liver resection in the UK.7 Patients with liver metastases usually have essentially normal liver function, but there is a significant risk of transient liver failure following major resection particularly in patients recently treated with chemotherapy. Although chronic liver disease is not an absolute contraindication to liver resection, the morbidity and mortality does increase with increasing hepatic dysfunction. Attempts at assessing hepatic functional reserve have been made including measurement of clearance of various dyes and metabolic substrates8 but there is no consensus as to the best method and none of these functional tests are routinely practiced. As with most major surgery, surgical experience and careful judgements based on pre and intraoperative findings are essential to a successful outcome. In order to select patients for resection and plan the surgical approach accurately, it is important to acquire sufficient information about the tumour site, size, number and relation to hepatic pedicles and the volume of tumour free functional parenchyma that will remain after resection. Preoperative
Functional liver anatomy Familiarity with the surgical anatomy of the liver is necessary to understand the principles of hepatic surgery. The liver is divided into functionally independent right and left lobes. Each lobe has its own blood supply from the hepatic artery and portal vein and its own venous and biliary drainage.2 The functional lobes are separated by an imaginary plane joining the gallbladder fossa to the inferior vena cava known as Cantlie’s line. The middle hepatic vein also demarcates the true right and left lobes. In the widely used Couinaud system, the liver is further divided into
Natalie Peel BSc MBChB MRCS is a Clinical Research Fellow at the University of Edinburgh and the Royal Infirmary of Edinburgh, UK. Conflicts of interest: none declared. Stephen Wigmore BSc MBBS MD FRCS is the Professor of Transplantation Surgery at the University of Edinburgh and the Royal Infirmary of Edinburgh, UK. Conflicts of interest: none declared.
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Ó 2011 Elsevier Ltd. All rights reserved.
HEPATOBILIARY SURGERY
imaging studies play a critical role in patient selection. Crosssectional imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography have an important role in enhancing the efficacy and safety of liver surgery. As a minimum all patients should undergo CT scanning prior to surgery; however the majority of patients also have an MRI scan as part of their preoperative assessment. CT scanning with contrast provides excellent detailed images of the liver, demonstrating tumour proximity to major pedicles and hepatic veins. CT is also useful in detecting extra-hepatic metastases in the abdomen, pelvis and lungs. MRI scanning is useful for visualizing vascular structures and their relation to the tumour and for characterizing the nature of the lesion. In recent years intraoperative ultrasound scanning (IOUS) has become a routine adjunct to preoperative imaging in liver surgery. This modality is capable of identifying occult lesions that preoperative imaging and palpation may miss. IOUS can also identify the patency of intrahepatic vessels and the presence of vascular invasion.4,9
effective, and surgeons are more confident at performing multiple non-anatomical or staged resections in responding patients. These non-anatomical resections are associated with a shorter operating time and preservation of functioning liver tissue. The advantages and disadvantages of anatomical and non-anatomical resections are outlined in Table 1. When planning the operation the aim is to leave two continuous segments with both an inflow and an outflow. This is achieved by removing an individual segment or by common anatomical resections as illustrated in Figure 1. It is generally accepted that, patients should proceed to surgery if they are considered fit, have resectable extra hepatic disease and will have least 25% of functional hepatic parenchyma remaining after resection. Larger resections are possible, but incur a high risk of inducing liver failure. Hepatocellular carcinoma (HCC) usually arises on a background of cirrhosis and patients tolerate resection of more than two segments poorly. Limited, parenchymal sparing operations should be favoured in these patients where possible. Studies suggest that most surgeons favour a 1-cm resection margin; however a study in 1989 found that in patients with HCC, so long as the margin was microscopically clear of tumour the size of the margin was not significant.14 Cirrhotic patients with large tumours are easier to treat than those with small, deep-seated tumours as less functional parenchyma needs to be removed with large volume tumours. Alternative therapy such as ablation or transplantation should be considered for small, deep-seated, awkward tumours.4 The improved safety of liver resections worldwide for cirrhotic patients is attributed to the combination of the acceptance of conservative resection margins and nonanatomical, parenchyma sparing operations.4 Metastatic neuroendocrine tumours are also best treated with non-anatomical resections as these are debulking rather that curative procedures.4
Choosing the right operation For primary liver tumours and colorectal metastases, liver resection remains the only potential curative treatment. A key decision in the planning of liver surgery is whether the resection should be anatomical or non-anatomical. For treatment of malignant disease, particularly large, deep-seated tumours, anatomical segmental resection is usually favoured. It enables resection of the parenchyma in areas distal to the tumour where vascular micro metastases are most likely to lie. In addition, anatomical resections are less likely to have positive margins and are associated with a lower incidence of intraoperative bleeding as fewer vessels lie in the interface between segments.4,9,10 One study that compared the incidence of positive margins in resection specimens found that non-anatomical resections were associated with a 16% rate compared with a 2% rate for anatomical operations.11 The standard resection margin has been 1 cm of normal parenchyma; however more recent studies have suggested that even margins of 1 mm are enough to achieve disease-free survival.9,12,13 In some cases the tumour’s close proximity to a major vascular structure will prevent a generous margin. In recent years, due to new chemotherapeutic agents, the type of liver resection performed to treat colorectal metastasis has changed significantly. Chemotherapy is now much more
Portal vein embolization For selected patients with liver cirrhosis or, for patients with a lesion in whom the liver remnant is considered too small to provide sufficient postoperative function, portal vein embolization (PVE) is an option. The portal vein is accessed on the side of the liver to be resected via a transhepatic percutaneous route. This is normally performed under radiological guidance. The vein is embolized approximately 4e6 weeks before the planned procedure in order to induce ipsilateral atrophy and contralateral hypertrophy in the liver remnant. The risk of tumour progression
Advantages and disadvantages of anatomical and non-anatomical liver resections
Advantages
Disadvantages
Non-anatomical
Anatomical
Conservation of functional liver tissue. Smaller operation. Opportunity for re-resection if necessary. May have smaller oncological clearance. Potential for greater incidence of bile leaks.
Greater oncological clearance of microscopic metastases or satellite lesions. Larger volume of functional liver tissue excised.
Table 1
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Figure 1 Common hepatic resections.
after PVE means that the shortest waiting time between intervention and operation would be preferable. A recent study has suggested that improvement in liver function after PVE occurs in advance of an increase in volume.15 In the future, liver resections after PVE may occur earlier than the 4e6 weeks currently practised. It would be expected that resection would be achievable in approximately half of those patients previously deemed unsuitable.9 There is evidence that this procedure is well tolerated and beneficial in patients with liver cirrhosis.16
devices salvage blood loss during an operation then wash, separate and reinfuse the red blood cells. Every effort is made to minimize blood loss and therefore reduce the necessity for transfusion. Studies have shown that in some centres more than 90% of all hepatectomies are now performed without any requirement for blood transfusions.17 Anaesthetic considerations Successful liver surgery with minimal blood loss is dependent on good communication between anaesthetist and surgeon. Apart from good surgical technique, blood loss is minimized if the patients’ CVP is maintained between 0 and 5 mmHg.9 This is achieved by restricted fluid administration and anaesthetic technique coupled with careful monitoring of urine output to ensure renal perfusion is not compromised.
Control of bleeding Liver resections can be complicated by bleeding particularly when the tumour is located close to major vascular structures. Blood loss during liver surgery has been found to correlate adversely with length of hospital stay, complication rate and long-term survival. There is now a wealth of data to support the limited use of blood transfusions.17,18 In some centres, patients are now encouraged to donate two units of autologous blood prior to a major hepatectomy. In other centres intra-operative blood salvage devices or cell savers are also routinely used in major liver resections to reduce the need for transfusion. These
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Vascular control Minimal blood loss in liver surgery is achieved by a combination of factors however, either inflow, or both inflow and outflow vascular control has been well illustrated to have a beneficial effect on outcome.17 Methods of hepatic vascular control involve occluding liver inflow either by clamping the portal triad, a major
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HEPATOBILIARY SURGERY
pedicle or a segmental branch depending on the position of the tumour and the extent of the planned resection. Total vascular occlusion, achieved by clamping both the inflow and outflow vessels is an alternative option used in some cases. Complete inflow occlusion of the portal triad is known as the Pringle manoeuvre (PM) and is the oldest and best established method of vascular control. The Pringle manoeuvre has physiological consequences that are well tolerated. Intermittent Pringle manoeuvre (IPM) is considered standard practice. Inflow is interrupted for a period of 10e15 minutes followed by unclamping for 5 minutes. IPM has been found to be preferable to constant clamping for several reasons. The cycle of Pringle on, Pringle off may reduce the incidence of IRI and could have a protective preconditioning effect.17 Clavien et al. demonstrated the protective effect of ischaemic preconditioning by clamping the portal triad for 10 minutes and reinstating flow for a further 10 minutes before clamping again for 30 minutes whilst performing a resection.19 This technique was found to be heptoprotective. The intermittent release of the clamp also allows gradual haemostasis during a prolonged period of time over smaller transaction areas. Finally the application of IPM can almost double the ischaemia time that can be safely achieved. A recent Cochrane Collaboration review on methods of vascular occlusion concluded that IPM was superior to PM as there was no increase in negative outcomes such as operating time or blood loss and that IPM had a protective effect particularly in cirrhotic livers.18 Total hepatic vascular exclusion (THVE) is rarely necessary but combines the Pringle manoeuvre with outflow occlusion. The IVC and major hepatic veins are clamped to isolate the liver completely from the systemic circulation. This technique decreases the risk of retrograde bleeding from the hepatic veins and the risk of air embolism.18 THVE has significant physiological consequences and is poorly tolerated. Clamping of the IVC causes a reduction in venous return of up to 60% and a reduction in cardiac output. To compensate, systemic vascular resistance and heart rate increase. Around 20% of patients, who are difficult to identify preoperatively, cannot tolerate this haemodynamic instability although this problem can be surmounted using veno-venous bypass. THVE is indicated for lesions infiltrating the cavohepatic junction or when IVC reconstruction must be performed however it is not routinely practiced. In comparisons with CPM it is associated with increased patient morbidity and increased hospital stay.18
stapler. CUSA has been widely accepted as an alternative to fracture technique. The CUSA is a small rod with a vibrating titanium tip that emits ultrasonic pressure waves which cavitate and appear to almost dissolve the parenchymal tissue. Vascular structures are spared as they have different water content and therefore fragment at a different suprasonic frequency.9 The water-jet dissector works in a similar fashion. A fine stream of high-pressure saline is used to dissect the liver parenchyma. The level of pressure cuts the parenchyma preserving the vessels. Radiofrequency ablation probes cause coagulative necrosis of the liver parenchyma and thrombosis and coagulation of small blood vessels whilst harmonic scalpels seal both parenchymal tissue and blood vessels as they cut. A recent systematic review of techniques for liver parenchymal transection concluded that although there is a lack of evidence in this area, there were no significant differences in morbidity or mortality of liver resection irrespective of the technique used.19 The clampecrush technique appeared to be quicker than others and up to six times cheaper and was recommended for these reasons.
Preventing postoperative blood loss The hepatic sinusoidal structure does not have smooth muscle capable of contracting to induce vasoconstriction.20 After the pathological section of the liver is resected a wide raw surface remains. Bleeding or bile leaks from this soft, friable surface are often difficult to manage. Technical progress has not obliterated the occurrence of such complications and meticulous surgery is still the most important factor in reducing patient morbidity. Any evidence of bile leakage or any actively bleeding vessel should be sutured. Oozing that continues from the cut surface can be dealt with by a number of different techniques. The argon beam coagulator is a noncontact, monopolar electrocoagulation device used in most surgical units to control bleeding from the raw edge of the liver. It transmits radiofrequency electrical energy from a hand-held electrode across a jet of argon gas. The argon gas jet clears the field of pooled blood and evenly distributes electrical energy to the target tissue. In addition to the argon beam, fibrin sealants are now widely used to achieve haemostasis. Fibrin sealants are derived from plasma components and mimic the stages of the blood coagulation process. Degradation and reabsorption of the resulting fibrin clot is achieved during normal wound healing and they are not associated with inflammation and tissue necrosis.20 Sealants are mainly delivered as a glue-like structure or impregnated in a collagen fleece or sponge which is laid onto the liver surface.20
Parenchymal dissection Liver parenchymal dissection does not proceed through bloodless planes. As methods to prevent blood loss are crucial to success in liver surgery a number of techniques have been developed to separate soft parenchyma from vascular and duct structures whilst minimizing blood loss. Techniques include the finger fracture technique, Kelly’s technique (clampecrush), ultrasonic dissector (cavitron ultrasonic surgical aspirator or CUSA), water-jet cutters, radiofrequency ablation probes (Habib probe) and harmonic scalpels.19 The finger fracture technique modified by using a Kelly clamp to crush the liver parenchyma is the oldest technique and is still widely used. The liver parenchyma is crushed to expose the vasculature which is controlled with ligatures, clips or a vascular
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Laparoscopic liver surgery Laparoscopic liver surgery is a developing field and experience is growing worldwide. A laparoscopic procedure is ideal for nonanatomical resections of tumours in segments two and three or on the inferior periphery of the liver as lesions in these regions are easily viewed at laparoscopy. Experienced centres have performed more major resections. Principles of vascular control are the same as in open surgery and parenchymal transection can be undertaken with ultrasonic dissectors and stapling devices. The view of the liver at laparoscopy can be excellent partly because positive intra abdominal pressure reduces bleeding intraoperatively. This,
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10 DeMatteo RP, Palese C, Jarnagin WR, Sun RL, Blumgart LH, Fong Y. Anatomic segmental hepatic resection is superior to wedge resection as an oncologic operation for colorectal liver metastases. J Gastrointest Surg 2000 MareApr; 4: 178e84. 11 Weber SM, Jarnagin WR, DeMatteo RP, Blumgart LH, Fong Y. Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 2000 Oct; 7: 643e50. 12 Ochiai T, Takayama T, Inoue K, et al. Hepatic resection with and without surgical margins for hepatocellular carcinoma in patients with impaired liver function. Hepatogastroenterology 1999 MayeJun; 46: 1885e9. 13 Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997 Mar; 15: 938e46. 14 Yoshida Y, Kanematsu T, Matsumata T, Takenaka K, Sugimachi K. Surgical margin and recurrence after resection of hepatocellular carcinoma in patients with cirrhosis. Further evaluation of limited hepatic resection. Ann Surg 1989 Mar; 209: 297e301. 15 de Graaf W, van Lienden KP, van den Esschert JW, Bennink RJ, van Gulik TM. Increase in future remnant liver function after preoperative portal vein embolization. Br J Surg 2011 Jun; 98: 825e34. doi:10.1002/bjs.7456. 16 Lee KC, Kinoshita H, Hirohashi K, Kubo S, Iwasa R. Extension of surgical indications for hepatocellular carcinoma by portal vein embolization. World J Surg 1993 JaneFeb; 17: 109e15. 17 Clavien PA, Yadav S, Sindram D, Bentley RC. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans. Ann Surg 2000 Aug; 232: 155e62. 18 Gurusamy KS, Sheth H, Kumar Y, Sharma D, Davidson BR. Pharmacological interventions versus no pharmacological intervention for ischaemia reperfusion injury in liver resection surgery performed under vascular control. Cochrane Database Syst Rev 2009 Oct 7; 4. CD007472. 19 Gurusamy KS, Pamecha V, Sharma D, Davidson BR. Techniques for liver parenchymal transection in liver resection. Cochrane Database Syst Rev 2009 Jan 21; 1. CD006880. 20 Berrevoet F, de Hemptinne B. Use of topical hemostatic agents during liver resection. Dig Surg 2007; 24: 288e93.
however, raises the risk of unidentified postoperative bleeding occurring from an unrecognized site when the pneumoperitoneum is relieved.
Conclusions Liver surgery when carried out in carefully selected patients has become a safe procedure. Patients should be selected by an experienced multidisciplinary team to ensure best outcomes. Minimizing blood loss and ischaemia reperfusion injury are keys to improving patient morbidity and mortality. A
REFERENCES 1 Schindl MJ, Redhead DN, Fearon KC, Garden OJ, Wigmore SJ. The value of residual liver volume as a predictor of hepatic dysfunction and infection after major liver resection. Gut 2005; 54: 289e96. 2 Ellis H, ed. Clinical anatomy. 9th Revised edn. Wiley-Blackwell, 1997. 3 Oliveira DA, Feitosa RQ, Correia MM. Segmentation of liver, its vessels and lesions from CT images for surgical planning. Biomed Eng Online 2011 Apr 20; 10: 30. 4 Cho CS, Park J, Fong Y. Hepatic resection. In: ACS Surgery: principles and practice. WebMD, Inc, 2007. 5 Fortner JC, Lincer RM. Hepatic resection in the elderly. Ann Surg 1990; 211: 141. 6 Karl RC, Smith SK, Fabri PJ. Validity of major cancer operations in elderly patients. Ann Surg Oncol 1995; 2: 107. 7 Scheele J, Stangl R, Altendorf-Hofmann A. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 1990 Nov; 77: 1241e6. 8 Lau H, Man K, Fan ST, Yu WC, Lo CM, Wong J. Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy. Br J Surg 1997 Sep; 84: 1255e9. 9 Hamady ZZ, Kotru A, Nishio H, Lodge JP. Current techniques and results of liver resection for colorectal liver metastases. Br Med Bull 2004 Oct 27; 70: 87e104.
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four sectors and eight segments.3 The right lobe is divided into an anterior and posterior sector by the right hepatic vein. The left lobe is divided into the medial and lateral sector by the left hepatic vein. The eight segments are numbered clockwise in a frontal plane (see Anatomy of the Liver on pp. 589e592 of this issue). Each segment is a functional, independent unit supplied by a single portal triad. The caudate lobe (segment I) is unique as it derives blood from both the right and left portal vein and hepatic artery. Couinaud’s classification of the liver provides crucial information as to the potential resection planes. Each segment functions as a self-contained unit. For the liver to remain viable, resections must proceed along the vessels that define the peripheries of the segments and therefore parallel the hepatic veins. The centrally located portal veins, bile ducts and hepatic arteries are preserved. The liver is surrounded by a fibrous capsule that was first described by Glisson in 1654.4 This fibrous capsule extends to surround the portal triads as they pass into the liver. The portal vein, hepatic artery and bile duct that run into each liver segment are surrounded by a substantial sheath.4 This is important as the fibrous sheath allows rapid control of inflow vessels to specific anatomical units within the liver and permits en masse occlusion of these vascular structures in what is known as the Pringle manoeuvre which will be discussed in more detail later.
Principles of liver surgery Natalie Peel Stephen Wigmore
Abstract In recent decades, liver resections have become safe operations for carefully selected patients. This article outlines the functional hepatic anatomy and discusses the choice of patient and operation. The principles to performing safe surgery with minimal blood loss will be addressed along with future advances.
Keywords Bleeding; embolization; hepatectomy; hepatic; liver; resection
Introduction For a variety of benign and malignant hepatic lesions, liver resection is the most appropriate treatment. The first elective liver surgery was performed in 1952 by Lortat-Jacob for the treatment of metastatic colorectal cancer, however major hepatectomies did not become standard practice until the 1980s. In recent decades, the morbidity and mortality associated with major liver resections has improved, and the indications for performing such operations have been refined making it a safe procedure in carefully selected patients. Resection of up to 75% of functional liver is now being performed in appropriate patients in several centres with a mortality that is as low as 2%.1 For those with malignant liver lesions, resection offers the best opportunity for long-term survival or cure and, for those with symptomatic benign tumours, resection is safe and effective. With the evolution of enhanced recovery programmes, the duration of hospitalization after hepatectomy is decreasing to less than 7 days in many centres with an expectation that all patients will regain normal hepatic function.
Choosing the right patient As with any major operation, preoperative assessment begins with a complete history and examination to determine the patient’s general health. Patients with risk factors should undergo detailed cardiopulmonary assessment. Antithrombotic medication such as warfarin or clopidogrel should be noted and arrangements made to stop treatment before admission to hospital. It is important to identify any underlying co-morbidities that would preclude a major liver resection. In the past, patients over the age of 70 years old were considered poor surgical candidates however several recent studies have shown that age in itself is not necessarily an obstacle to liver resection.5,6 Excision of colorectal metastasis is the most common reason for performing a liver resection in the UK.7 Patients with liver metastases usually have essentially normal liver function, but there is a significant risk of transient liver failure following major resection particularly in patients recently treated with chemotherapy. Although chronic liver disease is not an absolute contraindication to liver resection, the morbidity and mortality does increase with increasing hepatic dysfunction. Attempts at assessing hepatic functional reserve have been made including measurement of clearance of various dyes and metabolic substrates8 but there is no consensus as to the best method and none of these functional tests are routinely practiced. As with most major surgery, surgical experience and careful judgements based on pre and intraoperative findings are essential to a successful outcome. In order to select patients for resection and plan the surgical approach accurately, it is important to acquire sufficient information about the tumour site, size, number and relation to hepatic pedicles and the volume of tumour free functional parenchyma that will remain after resection. Preoperative
Functional liver anatomy Familiarity with the surgical anatomy of the liver is necessary to understand the principles of hepatic surgery. The liver is divided into functionally independent right and left lobes. Each lobe has its own blood supply from the hepatic artery and portal vein and its own venous and biliary drainage.2 The functional lobes are separated by an imaginary plane joining the gallbladder fossa to the inferior vena cava known as Cantlie’s line. The middle hepatic vein also demarcates the true right and left lobes. In the widely used Couinaud system, the liver is further divided into
Natalie Peel BSc MBChB MRCS is a Clinical Research Fellow at the University of Edinburgh and the Royal Infirmary of Edinburgh, UK. Conflicts of interest: none declared. Stephen Wigmore BSc MBBS MD FRCS is the Professor of Transplantation Surgery at the University of Edinburgh and the Royal Infirmary of Edinburgh, UK. Conflicts of interest: none declared.
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imaging studies play a critical role in patient selection. Crosssectional imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography have an important role in enhancing the efficacy and safety of liver surgery. As a minimum all patients should undergo CT scanning prior to surgery; however the majority of patients also have an MRI scan as part of their preoperative assessment. CT scanning with contrast provides excellent detailed images of the liver, demonstrating tumour proximity to major pedicles and hepatic veins. CT is also useful in detecting extra-hepatic metastases in the abdomen, pelvis and lungs. MRI scanning is useful for visualizing vascular structures and their relation to the tumour and for characterizing the nature of the lesion. In recent years intraoperative ultrasound scanning (IOUS) has become a routine adjunct to preoperative imaging in liver surgery. This modality is capable of identifying occult lesions that preoperative imaging and palpation may miss. IOUS can also identify the patency of intrahepatic vessels and the presence of vascular invasion.4,9
effective, and surgeons are more confident at performing multiple non-anatomical or staged resections in responding patients. These non-anatomical resections are associated with a shorter operating time and preservation of functioning liver tissue. The advantages and disadvantages of anatomical and non-anatomical resections are outlined in Table 1. When planning the operation the aim is to leave two continuous segments with both an inflow and an outflow. This is achieved by removing an individual segment or by common anatomical resections as illustrated in Figure 1. It is generally accepted that, patients should proceed to surgery if they are considered fit, have resectable extra hepatic disease and will have least 25% of functional hepatic parenchyma remaining after resection. Larger resections are possible, but incur a high risk of inducing liver failure. Hepatocellular carcinoma (HCC) usually arises on a background of cirrhosis and patients tolerate resection of more than two segments poorly. Limited, parenchymal sparing operations should be favoured in these patients where possible. Studies suggest that most surgeons favour a 1-cm resection margin; however a study in 1989 found that in patients with HCC, so long as the margin was microscopically clear of tumour the size of the margin was not significant.14 Cirrhotic patients with large tumours are easier to treat than those with small, deep-seated tumours as less functional parenchyma needs to be removed with large volume tumours. Alternative therapy such as ablation or transplantation should be considered for small, deep-seated, awkward tumours.4 The improved safety of liver resections worldwide for cirrhotic patients is attributed to the combination of the acceptance of conservative resection margins and nonanatomical, parenchyma sparing operations.4 Metastatic neuroendocrine tumours are also best treated with non-anatomical resections as these are debulking rather that curative procedures.4
Choosing the right operation For primary liver tumours and colorectal metastases, liver resection remains the only potential curative treatment. A key decision in the planning of liver surgery is whether the resection should be anatomical or non-anatomical. For treatment of malignant disease, particularly large, deep-seated tumours, anatomical segmental resection is usually favoured. It enables resection of the parenchyma in areas distal to the tumour where vascular micro metastases are most likely to lie. In addition, anatomical resections are less likely to have positive margins and are associated with a lower incidence of intraoperative bleeding as fewer vessels lie in the interface between segments.4,9,10 One study that compared the incidence of positive margins in resection specimens found that non-anatomical resections were associated with a 16% rate compared with a 2% rate for anatomical operations.11 The standard resection margin has been 1 cm of normal parenchyma; however more recent studies have suggested that even margins of 1 mm are enough to achieve disease-free survival.9,12,13 In some cases the tumour’s close proximity to a major vascular structure will prevent a generous margin. In recent years, due to new chemotherapeutic agents, the type of liver resection performed to treat colorectal metastasis has changed significantly. Chemotherapy is now much more
Portal vein embolization For selected patients with liver cirrhosis or, for patients with a lesion in whom the liver remnant is considered too small to provide sufficient postoperative function, portal vein embolization (PVE) is an option. The portal vein is accessed on the side of the liver to be resected via a transhepatic percutaneous route. This is normally performed under radiological guidance. The vein is embolized approximately 4e6 weeks before the planned procedure in order to induce ipsilateral atrophy and contralateral hypertrophy in the liver remnant. The risk of tumour progression
Advantages and disadvantages of anatomical and non-anatomical liver resections
Advantages
Disadvantages
Non-anatomical
Anatomical
Conservation of functional liver tissue. Smaller operation. Opportunity for re-resection if necessary. May have smaller oncological clearance. Potential for greater incidence of bile leaks.
Greater oncological clearance of microscopic metastases or satellite lesions. Larger volume of functional liver tissue excised.
Table 1
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Figure 1 Common hepatic resections.
after PVE means that the shortest waiting time between intervention and operation would be preferable. A recent study has suggested that improvement in liver function after PVE occurs in advance of an increase in volume.15 In the future, liver resections after PVE may occur earlier than the 4e6 weeks currently practised. It would be expected that resection would be achievable in approximately half of those patients previously deemed unsuitable.9 There is evidence that this procedure is well tolerated and beneficial in patients with liver cirrhosis.16
devices salvage blood loss during an operation then wash, separate and reinfuse the red blood cells. Every effort is made to minimize blood loss and therefore reduce the necessity for transfusion. Studies have shown that in some centres more than 90% of all hepatectomies are now performed without any requirement for blood transfusions.17 Anaesthetic considerations Successful liver surgery with minimal blood loss is dependent on good communication between anaesthetist and surgeon. Apart from good surgical technique, blood loss is minimized if the patients’ CVP is maintained between 0 and 5 mmHg.9 This is achieved by restricted fluid administration and anaesthetic technique coupled with careful monitoring of urine output to ensure renal perfusion is not compromised.
Control of bleeding Liver resections can be complicated by bleeding particularly when the tumour is located close to major vascular structures. Blood loss during liver surgery has been found to correlate adversely with length of hospital stay, complication rate and long-term survival. There is now a wealth of data to support the limited use of blood transfusions.17,18 In some centres, patients are now encouraged to donate two units of autologous blood prior to a major hepatectomy. In other centres intra-operative blood salvage devices or cell savers are also routinely used in major liver resections to reduce the need for transfusion. These
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Vascular control Minimal blood loss in liver surgery is achieved by a combination of factors however, either inflow, or both inflow and outflow vascular control has been well illustrated to have a beneficial effect on outcome.17 Methods of hepatic vascular control involve occluding liver inflow either by clamping the portal triad, a major
624
Ó 2011 Elsevier Ltd. All rights reserved.
HEPATOBILIARY SURGERY
pedicle or a segmental branch depending on the position of the tumour and the extent of the planned resection. Total vascular occlusion, achieved by clamping both the inflow and outflow vessels is an alternative option used in some cases. Complete inflow occlusion of the portal triad is known as the Pringle manoeuvre (PM) and is the oldest and best established method of vascular control. The Pringle manoeuvre has physiological consequences that are well tolerated. Intermittent Pringle manoeuvre (IPM) is considered standard practice. Inflow is interrupted for a period of 10e15 minutes followed by unclamping for 5 minutes. IPM has been found to be preferable to constant clamping for several reasons. The cycle of Pringle on, Pringle off may reduce the incidence of IRI and could have a protective preconditioning effect.17 Clavien et al. demonstrated the protective effect of ischaemic preconditioning by clamping the portal triad for 10 minutes and reinstating flow for a further 10 minutes before clamping again for 30 minutes whilst performing a resection.19 This technique was found to be heptoprotective. The intermittent release of the clamp also allows gradual haemostasis during a prolonged period of time over smaller transaction areas. Finally the application of IPM can almost double the ischaemia time that can be safely achieved. A recent Cochrane Collaboration review on methods of vascular occlusion concluded that IPM was superior to PM as there was no increase in negative outcomes such as operating time or blood loss and that IPM had a protective effect particularly in cirrhotic livers.18 Total hepatic vascular exclusion (THVE) is rarely necessary but combines the Pringle manoeuvre with outflow occlusion. The IVC and major hepatic veins are clamped to isolate the liver completely from the systemic circulation. This technique decreases the risk of retrograde bleeding from the hepatic veins and the risk of air embolism.18 THVE has significant physiological consequences and is poorly tolerated. Clamping of the IVC causes a reduction in venous return of up to 60% and a reduction in cardiac output. To compensate, systemic vascular resistance and heart rate increase. Around 20% of patients, who are difficult to identify preoperatively, cannot tolerate this haemodynamic instability although this problem can be surmounted using veno-venous bypass. THVE is indicated for lesions infiltrating the cavohepatic junction or when IVC reconstruction must be performed however it is not routinely practiced. In comparisons with CPM it is associated with increased patient morbidity and increased hospital stay.18
stapler. CUSA has been widely accepted as an alternative to fracture technique. The CUSA is a small rod with a vibrating titanium tip that emits ultrasonic pressure waves which cavitate and appear to almost dissolve the parenchymal tissue. Vascular structures are spared as they have different water content and therefore fragment at a different suprasonic frequency.9 The water-jet dissector works in a similar fashion. A fine stream of high-pressure saline is used to dissect the liver parenchyma. The level of pressure cuts the parenchyma preserving the vessels. Radiofrequency ablation probes cause coagulative necrosis of the liver parenchyma and thrombosis and coagulation of small blood vessels whilst harmonic scalpels seal both parenchymal tissue and blood vessels as they cut. A recent systematic review of techniques for liver parenchymal transection concluded that although there is a lack of evidence in this area, there were no significant differences in morbidity or mortality of liver resection irrespective of the technique used.19 The clampecrush technique appeared to be quicker than others and up to six times cheaper and was recommended for these reasons.
Preventing postoperative blood loss The hepatic sinusoidal structure does not have smooth muscle capable of contracting to induce vasoconstriction.20 After the pathological section of the liver is resected a wide raw surface remains. Bleeding or bile leaks from this soft, friable surface are often difficult to manage. Technical progress has not obliterated the occurrence of such complications and meticulous surgery is still the most important factor in reducing patient morbidity. Any evidence of bile leakage or any actively bleeding vessel should be sutured. Oozing that continues from the cut surface can be dealt with by a number of different techniques. The argon beam coagulator is a noncontact, monopolar electrocoagulation device used in most surgical units to control bleeding from the raw edge of the liver. It transmits radiofrequency electrical energy from a hand-held electrode across a jet of argon gas. The argon gas jet clears the field of pooled blood and evenly distributes electrical energy to the target tissue. In addition to the argon beam, fibrin sealants are now widely used to achieve haemostasis. Fibrin sealants are derived from plasma components and mimic the stages of the blood coagulation process. Degradation and reabsorption of the resulting fibrin clot is achieved during normal wound healing and they are not associated with inflammation and tissue necrosis.20 Sealants are mainly delivered as a glue-like structure or impregnated in a collagen fleece or sponge which is laid onto the liver surface.20
Parenchymal dissection Liver parenchymal dissection does not proceed through bloodless planes. As methods to prevent blood loss are crucial to success in liver surgery a number of techniques have been developed to separate soft parenchyma from vascular and duct structures whilst minimizing blood loss. Techniques include the finger fracture technique, Kelly’s technique (clampecrush), ultrasonic dissector (cavitron ultrasonic surgical aspirator or CUSA), water-jet cutters, radiofrequency ablation probes (Habib probe) and harmonic scalpels.19 The finger fracture technique modified by using a Kelly clamp to crush the liver parenchyma is the oldest technique and is still widely used. The liver parenchyma is crushed to expose the vasculature which is controlled with ligatures, clips or a vascular
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Laparoscopic liver surgery Laparoscopic liver surgery is a developing field and experience is growing worldwide. A laparoscopic procedure is ideal for nonanatomical resections of tumours in segments two and three or on the inferior periphery of the liver as lesions in these regions are easily viewed at laparoscopy. Experienced centres have performed more major resections. Principles of vascular control are the same as in open surgery and parenchymal transection can be undertaken with ultrasonic dissectors and stapling devices. The view of the liver at laparoscopy can be excellent partly because positive intra abdominal pressure reduces bleeding intraoperatively. This,
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10 DeMatteo RP, Palese C, Jarnagin WR, Sun RL, Blumgart LH, Fong Y. Anatomic segmental hepatic resection is superior to wedge resection as an oncologic operation for colorectal liver metastases. J Gastrointest Surg 2000 MareApr; 4: 178e84. 11 Weber SM, Jarnagin WR, DeMatteo RP, Blumgart LH, Fong Y. Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 2000 Oct; 7: 643e50. 12 Ochiai T, Takayama T, Inoue K, et al. Hepatic resection with and without surgical margins for hepatocellular carcinoma in patients with impaired liver function. Hepatogastroenterology 1999 MayeJun; 46: 1885e9. 13 Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997 Mar; 15: 938e46. 14 Yoshida Y, Kanematsu T, Matsumata T, Takenaka K, Sugimachi K. Surgical margin and recurrence after resection of hepatocellular carcinoma in patients with cirrhosis. Further evaluation of limited hepatic resection. Ann Surg 1989 Mar; 209: 297e301. 15 de Graaf W, van Lienden KP, van den Esschert JW, Bennink RJ, van Gulik TM. Increase in future remnant liver function after preoperative portal vein embolization. Br J Surg 2011 Jun; 98: 825e34. doi:10.1002/bjs.7456. 16 Lee KC, Kinoshita H, Hirohashi K, Kubo S, Iwasa R. Extension of surgical indications for hepatocellular carcinoma by portal vein embolization. World J Surg 1993 JaneFeb; 17: 109e15. 17 Clavien PA, Yadav S, Sindram D, Bentley RC. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans. Ann Surg 2000 Aug; 232: 155e62. 18 Gurusamy KS, Sheth H, Kumar Y, Sharma D, Davidson BR. Pharmacological interventions versus no pharmacological intervention for ischaemia reperfusion injury in liver resection surgery performed under vascular control. Cochrane Database Syst Rev 2009 Oct 7; 4. CD007472. 19 Gurusamy KS, Pamecha V, Sharma D, Davidson BR. Techniques for liver parenchymal transection in liver resection. Cochrane Database Syst Rev 2009 Jan 21; 1. CD006880. 20 Berrevoet F, de Hemptinne B. Use of topical hemostatic agents during liver resection. Dig Surg 2007; 24: 288e93.
however, raises the risk of unidentified postoperative bleeding occurring from an unrecognized site when the pneumoperitoneum is relieved.
Conclusions Liver surgery when carried out in carefully selected patients has become a safe procedure. Patients should be selected by an experienced multidisciplinary team to ensure best outcomes. Minimizing blood loss and ischaemia reperfusion injury are keys to improving patient morbidity and mortality. A
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