Principles of Hepatic Surgery

• The morphologic anatomy of the liver, based on superficial landmarks, has been replaced by functional anatomy, which is more appropriate for liver surgery.

• The liver is divided according to portal pedicles and hepatic veins. Cantlie’s line(where the middle hepatic vein is located) divides the liver in right and left hemilivers.

• The right hemiliver is divided in anterior (segments 5 and 8) and posterior (segments 6 and 7) sectors by a plan where the right hepatic vein is located.

• The left hemiliver is divided in medial (segment 4) and lateral (segments 2 and 3)sectors.

• Segment 1 corresponds to the caudate lobe, located around the vena cava.

• Vascular and biliary variations are very frequent and they have significant implications on liver resections and/or transplantation.

• Perioperative imaging is fundamental in modern hepatic surgery. Accurate knowledge of the regular anatomy of the liver and its variations is essential for planninghepatectomy or transplantation.

• A minority of patients has the classical vascular and/or biliary anatomy and somenormal radiological findings can be misinterpreted as disease.

• The liver is divided in two hemi-livers by a sagittal plane from the gallbladder fossa to the inferior vena cava. The Cantlie line is better delimited by radiology andincludes the middle hepatic vein.

• Modern multislice computed tomography can scan the whole liver in 5-10s andprovides precise parenchymal and vascular anatomy using three phases (arterial,portal, and venous).

• Magnetic Resonance Imaging (MRI) is free of ionizing radiation and especially usefulto evaluate focal and diffuse parenchymal diseases. Cholangio MRI plays a majorrole in the assessment of the biliary tree.

• Intraoperative ultrasound (IOUS) is a fundamental tool used in modern hepatic surgery, which can precisely define the liver anatomy and accurately identify target lesions.

• IOUS is one of the key factors to spare hepatic parenchyma without compromising the oncological endpoints.

• IOUS should be performed by the first surgeon with the aim of gathering information that might impact the surgical strategy.

• IOUS is an important tool for staging malignancies, determining resectability, and planning the most adequate procedure.

• Contrast-enhanced IOUS (CEIOUS) is useful in the differential diagnosis of new lesions eventually detected with basic IOUS and can increase its overall sensitivity.

• The function and the volume of the residual liver should be assessed prior to a hepatectomy. Combinations of imaging and blood samples are currently used to assessliver function but no optimal screening for liver injury exists. Thus, pre-resection biopsy may be indicated in selected cases. Volumetry based on imaging is used to estimate residual liver volume and can be used for treatment decision. Volumetry before and after portal vein embolization (PVE) also reveals the regenerative potential, a marker of underlying liver injury.

• Cirrhosis, a common finding in patients with primary liver malignancies, limits the extent of resection. Preoperative chemotherapy may cause different types of liver injury associated with adverse outcome events after liver resection.

• Non-alcoholic fatty liver disease (NAFLD) is associated with the use of irinotecan-based chemotherapy and features of metabolic syndrome. Sinusoidal liver injury occurs in 19-50% after preoperative treatment with oxaliplatin-based chemotherapy, and is associated with increased postoperative morbidity. Bevacizumab has oncological benefits in the treatment of colorectal liver metastases when administered together with oxaliplatin, and protects against oxaliplatin-induced sinusoidal injury.

• Regarding the volume of the future liver remnant (FLR), the following are suggested:>40% in patients with cirrhosis; >30% in patients who receive more than three months of preoperative chemotherapy; >20% in the normal liver.

• The main goals of liver function assessment before and after hepatic resection are ultimately prevention and early detection of postoperative liver failure (PLF).

• The minimal required volume of remnant liver parenchyma after resection is proportional to severity of parenchyma injury. Thus, both liver volumes and function tests should be assessed preoperatively.

• The estimate of remaining liver volume is usually enough to predict the risk of PLF in patients without underlying chronic liver disease. However, adequate evaluation of hepatic function in the presence of chronic underlying liver disease (i.e. cirrhosis,chronic hepatitis, chemotherapy associated liver injury, etc.) is complex. Most available tests evaluate only one or few of the multiple liver functions and rarely take into account regional variations of underlying disease severity.

• Clinical scores, such as the Child-Turcotte system and Model for End-Stage Liver Disease (MELD), combine several biochemical and clinical parameters and have variable ability to predict PLF. Indocyanine green retention test (a dynamic quantitative test) is among the most commonly used tests in the Orient, and it is incorporated in a commonly used algorithm in Japan. Molecular nuclear imaging techniques, such as 99mTC-labeled galactosyl human serum albumin (GSA) scintigraphy, have been used pre- and postoperatively to estimate functional hepatocyte volume. Associated CT images can provide functional evaluation of each hepatic region.

• Transient liver dysfunction is expected after partial hepatectomy, but severe liver function tests deterioration and/or delayed recovery should raise concern for PLF.

• The number of patients with cirrhosis requiring liver surgery is increasing, with hepatocellular carcinoma being the major indication. The mortality rate of cirrhotic patients is –two to three times higher than that of non-cirrhotic patients.

• Preoperative assessment and risk stratification are challenging. Attention should be paid to liver function, portal hypertension, and systemic conditions including nutritional status.

• Low central venous pressure, anterior approach, and vascular occlusion are useful strategies to reduce bleeding during hepatectomies on cirrhotic patients. Also, laparoscopic resections can minimize some postoperative complications, mainly ascites.

• Fresh frozen plasma and/or albumin, as well as diuretics, are useful in the management of postoperative ascites, which occurs in more than a third of patients.Postoperative liver failure is associated with very high mortality and should be early recognized for proper management.

• Portal vein occlusion, through portal vein embolization or portal vein ligation, is a strategy used to induce hypertrophy of the future remnant liver (FRL) before extended hepatic resections.

• The ordinary indications for portal vein occlusion are: i) FRL ≤20% of the total liver volume in healthy hepatic parenchyma, ii) FRL ≤30% of the total liver volume inpatients submitted to systemic chemotherapy, and iii) FRL ≤40% of the total liver volume in the presence of chronic hepatic disease.

• Transarterial chemoembolization (TACE) is an effective palliative treatment for hepatocellular carcinoma (HCC) and the standard of care for unresectable HCCs. Randomized trials have shown long-term survival advantages with TACE when compared to best supportive care.

• TACE is an attractive palliative therapy for other tumors, such as intrahepatic cholangio carcinoma and metastatic disease from a variety of primaries (ocular melanoma, colorectal cancer, breast cancer, neuroendocrine tumors, renal cell carcinoma, and abdominal sarcomas).

• Hepatic malignancies can be destroyed through chemical or thermal ablation. Radiofrequency ablation and ethanol injection, percutaneous or intraoperative, are the most commonly used methods of local ablation for hepatocellular carcinoma and liver metastases. Results are promising but inferior to liver resection or transplantation.

• Anesthetic management plays a key role in the reduction of perioperative causes of mortality in liver surgery, such as bleeding and liver failure.

• Intraoperative reduction of the hepatic blood flow can result from changes in blood volume status and also from mechanical or pharmacological effects, and can lead to liver dysfunction.

• Central venous pressure lower than 5mmHg reduces blood loss during hepatic parenchymal transection.

• Inhalational anesthetics such as sevoflurane, desflurane, and isoflurane can maintainor even increase total hepatic blood flow; meanwhile, intravenous anesthetics have a modest impact on that.

• Intraoperative fluid management should not be guided exclusively by central venous pressure, and the use of colloids (such as 5% albumin) as a maintenance and replacement solution reduces extravascular translocation of fluids.

• Pharmacological preconditioning, mainly with the use of inhaled anesthetics, has been used to prevent ischemia-reperfusion syndrome, although its pathophysiology is not entirely understood.

• The historical high morbidity and mortality rates associated with liver resections has decreased significantly over time. The pattern of complications has also changed.Massive intraoperative blood loss has become very rare, but other complications such as bile leak remain high.

• Modern methods to prevent blood loss, especially allogeneic blood transfusion,include the use of intraoperative low central venous pressure, various methods of vascular clamping, intraoperative blood salvage, preoperative autologous donation,acute intraoperative normovolemic hemodilution, and efficient modalities of parenchymal transection.

• Postoperative liver failure is one of the most serious complications after a hepatectomy. Although uncommon, it is associated with high mortality. Knowledge of risk factors is crucial because prevention is the best approach to avoid mortality. However, early identification of liver failure allows for some effective measures.

• Bile leak is the most common biliary complication after liver resections. Most resolve with conservative approaches, and the need for surgical approach is associated with higher mortality rates. Proper intraoperative detection and closure of bile leaks is essential to prevent postoperative biliary fistula.

• The liver is the most common site of metastases from colorectal cancer, and complete resection of colorectal liver metastases (CLM) is the only potentially curative treatment.

• Resection of CLM is associated with low operative mortality and long-term survival has improved, with 5-year survival rates exceeding 50%.

• Besides a potential effect on survival, preoperative chemotherapy can increase the resection rate and improve patient selection. Despite no clear benefits for initially resectable CLM, neoadjuvant chemotherapy has a crucial role in initially unresectable disease.

• Surgical strategies, such as preoperative portal vein embolization, two-stage hepatectomy and resection combined with ablation, have enabled surgical resection of multiple bilateral CLM.

• Selected patients with extrahepatic disease, mainly lung metastases, have been considered for curative resection with substantial increases in overall survival.

• Synchronous CLM can be resected after, simultaneously with, or before resection of the primary cancer, according mainly to location, symptoms, and extent of colorectal cancer and hepatic metastases. Simultaneous resection should be avoided if major resections are required for both primary and hepatic diseases.

• Surgery for hepatic recurrence of CLM results in similar overall survival to that associated with first hepatic resection, and curative surgery should be considered for each relapse.

• Neuroendocrine liver metastases (NELMs) occur in 50-95% of endocrine tumors and represent the main cause of death. Management of NELMs is challenging and should take into account factors such as the tumor biological behavior, the presence of symptoms, and the age and performance status of the patient.

• Different therapeutic options (such as partial hepatectomy, liver transplantation, non-surgical liver directed therapies, and systemic treatments) can be used alone or in combination.

• Surgical resection remains the gold standard and the only potentially curative treatment for NELMs. Despite high recurrence rates, partial hepatectomy is performed with curative intent (in a minority of patients due to the high frequency of multiple and bilateral metastases) or for control of symptoms. Partial hepatectomy is usually indicated in patients with no extrahepatic disease when at least 90% of tumor burden can be resected.

• The role of liver transplantation (LT) for NELMs remains unclear and established selection criteria are lacking. Reasons to support LT are the usual indolent tumor behavior, tendency to metastatize to the liver, reduced possibilities for curative intention partial hepatectomy, and high recurrence rates after partial hepatectomy. Liver transplant should be considered in carefully selected patients with unresectable NELMs confined to the liver.

• The dogma “there is no role for the surgical treatment of liver metastases from non-colorectal non-neuroendocrine tumors” is no longer valid.

• There are no guidelines for the management of non-colorectal non-neuroendocrine liver metastases and the complex decision management should be done by a multidisciplinary tumor board.

• The variety of clinical situations, like individual tumor site and histology, patient age, disease-free interval between treatment of the primary tumor and diagnosis of the metastases, intrahepatic tumor burden, response to chemotherapy, and the presence of extrahepatic disease should be considered in the surgical management of non-colorectal non-neuroendocrine liver metastases.

• In general, liver resection of non-colorectal non-neuroendocrine liver metastases should be considered in patients with well-controlled disease or responding to chemotherapy.

• Hepatic resection of non-colorectal non-neuroendocrine liver metastases is a safe,feasible, and effective treatment.

• Selected patients with non-colorectal non-neuroendocrine liver metastases can have similar survival to their colorectal cancer counterparts.

• Hepatocellular carcinoma (HCC) is effectively a wide range of diseases, occurring in a wide range of underlying liver diseases. The combination of these problems requires attention to details of tumor location, extent and anatomy, as well as attention to subtleties of liver function limitations and variable causes of the underlying liver diseases.

• Most patients have competing causes of death - HCC and underlying liver disease- and treatment of the cancer is impacted by existing liver disease/dysfunction.

• Given the wide range of etiologies and underlying liver conditions, presentation canvary from an incidental finding, to a fever, to mass effect of massive tumor, to signs of liver dysfunction, to paraneoplastic syndromes.

• Several staging systems for HCC take into account tumor factors and liver factors relevant to prognosis among candidates for treatment and those best treated with supportive care.

• Among interventional therapies, intra-arterial therapies, percutaneous ablative therapies, and more aggressive potentially curative therapies (partial hepatectomy or liver transplantation) reflect the wide range of presentations and problems with small tumors in advanced liver disease patients vs. extensive cancer in patients with preserved underlying liver function.

• Proper management of HCC patients thus requires deep and expansive multi- and inter-disciplinary care designed to apply the best options to individual patients.

• Hilar cholangiocarcinoma is a complex disease for which the only curative treatment is complete surgical resection.

• Staging and evaluation of resectability of hilar cholangiocarcinoma require preoperative determination of tumor extent to the biliary tract, portal vein, and hepatic artery.

• R0 resection is of utmost importance and has been associated with improved survival.Major hepatic resection is needed to achieve complete longitudinal and radial negative margins. Portal vein involvement and bilateral biliary extent to secondary branches are not contraindications for curative intent surgery.

• Preoperative portal vein embolization and selective or total biliary drainage are available tools to increase resectability rate and minimize surgical morbidity.

• Orthotopic liver transplantation can benefit a subgroup of patients with unresectable small hilar cholangiocarcinoma.

• Palliative therapies include surgical biliary drainage procedures, endoscopic orpercutaneous bile duct stenting, and local ablative methods (such as chemotherapy and photodynamic therapy).

• Clinical presentation and management of intrahepatic cholangiocarcinoma (IHCC),the second most frequent primary liver tumor (after hepatocellular carcinoma), depend on the location of origin (juxtahilar to end-order biliary branches).

• In addition to classical risk factors for IHCC (such as parasitic infections, bile ductectasia, and primary sclerosing cholangitis), hepatitis B and C virus infection,cirrhosis, obesity, diabetes, and genetic polymorphisms seem to play a role in IHC Corigin.

• The three pathological subtypes – mass-forming, periductal-infiltrating, and intraductal-growth tumors – present different biological behavior and imaging characteristics.

• Surgical resection of IHCCs carries high morbidity and mortality rates, but it is currently the only curative treatment for IHCC, with a 5-year overall survival rate of 27%. Recurrence is frequent, rarely amenable for repeat surgery, and usually associated with death. The role of liver transplantation is controversial.

• Gallbladder (GB) carcinoma is 5th most common malignancy of the gastrointestinal tract and its incidence varies widely worldwide. Long-term survival can only be achieved with complete surgical resection, which is guided by the T stage.

• In early GB cancer T1a tumors can be treated with a simple cholecystectomy while T1b or T2 tumors demand an extended cholecystectomy (associated or not with bile duct resection). Advanced GB cancer (T3 or T4) usually requires extended major hepatectomy and common bile duct resection and reconstruction.Associated regional lymphadenectomy has potential therapeutic and prognostic benefits.

• Radical surgery has no proven benefit in metastatic disease (including lymphnodes outside the hepatoduodenal ligament).

• The high rate of recurrence after curative resection of GB carcinoma justifies the use of adjuvant therapy (except for T1 disease), despite the scarcity of data.

• The majority of patients with GB carcinomas present with advanced disease and palliative treatment of symptomatic jaundice, pain, or gastrointestinal obstruction is frequently required.

• The most common malignant hepatic tumor is by far hepatocellular carcinoma, followed by intrahepatic cholangiocarcinoma. However, other primary malignancies can occur and require specific approaches.

• Cystadenocarcinoma is a cystic tumor that usually develops from hepatic biliary cystadenoma. In both cases, radical surgical resection is the treatment of choice.

• Primary hepatic lymphomas are very rare (contrary to the frequent secondary involvement of the liver in disseminated non-Hodgkin lymphoma) and frequently associated with hepatitis C virus infection. Chemotherapy is efficient for most tumors and surgical resection indicated for complete resection of limited tumors or to reduce tumor burden before systemic therapy.

• Most cases of hepatoblastoma occur in childhood. Prognosis in adults is much poorer due to late diagnosis. Treatment is based on complete surgical resection.

• Hepatic epithelioid hemangioendothelioma is a rare vascular tumor with variable degrees of aggressiveness. Surgical resection (including liver transplantation) is the best approach when no extrahepatic involvement is present.

• Angiosarcoma, the most common primary hepatic sarcoma, represents up to 2%of primary liver malignancies, occurs more frequently in aged patients, and carries a very poor prognosis. Surgical resection is the best option in resectable cases, although recurrence is very common. Chemotherapy and trans-arterial therapy are used alone (to prevent bleeding and avoid tumor growth) or in combination with surgery.

• Hemangioma (the most common benign solid hepatic tumor) and Focal NodularHyperplasia (FNH) seldom pose a clinical significant risk requiring a surgical procedure.

• Hepatic adenoma is a rare tumor that may cause significant morbidity from bleeding, rupture, or malignant transformation. It represents the most frequent indication for surgical intervention among solid benign hepatic tumors.

• Oral contraceptives have been associated with hepatic adenoma and FNH. Nonetheless this association is not clear for hepatic hemangiomas.

• Other benign solid tumors are of exceedingly low frequency. They are difficult to diagnose and exceptionally require surgical treatment.

• Despite most of hepatic incidentalomas in patients with and without known cancer are benign, some of them require follow-up or treatment and management of incidentalomas is challenging.

• Non-parasitic cystic lesions of the liver are common (up to 5-20% of the population), mainly simple cysts, and increasing in incidence with age. Most of them are asymptomatic and diagnosed incidentally at abdominal surgery or radiological studies for unrelated disease.

• Symptomatic simple cysts and polycystic liver disease are frequently treated by deroofing or partial hepatectomy (associated or not with deroofing of residual cysts). In selected cases, liver transplantation can represent the only definitive treatment, especially if portal hypertension or cirrhosis is present. Percutaneous aspiration, with or without sclerotherapy, can be useful to determine if symptoms are related to the cysts to be treated, or it can be used rarely as a definitive treatment (when associated with sclerotherapy).

• Neoplastic cysts include benign biliary cystadenoma and cystadenocarcinoma. Cystadenoma originates from intrahepatic bile ducts and may undergo malignant transformation to biliary cystadenocarcinoma, and therefore require more aggressive management.

• Cystic biliary dilatation of Caroli’s disease is frequently associated with complications, especially hepatolithiasis and recurrent cholangitis. Liver resection is the treatment of choice for unilobar disease, and it can be associated with contra-lateral clearance of stones in bilobar disease. Treatment of diffuse disease is challenging, sometimes requiring liver transplantation as a definitive treatment.

• Other rare cystic lesions of the liver include cystic metastases or primary tumors and post-traumatic cysts among others. They should have individualized treatment.

• The most common parasitic hepatic disease that can need surgical treatment is the hydatid cyst, caused by Echinococcus granulosus. Other echinococcosis (alveolar and polycystic) are less frequent.

• Hydatid cysts may be multiple and can measure up to 20-50 cm in diameter. Most of them develop in the right lobe of the liver. Commonly, symptoms result from mass effect or cystic complications, such as rupture (into biliary tract, peritoneal cavity, hollow viscera, and lungs) or infection. Diagnosis is suggested especially by radiological findings.

• Surgical treatment can be conservative (comprising sterilization of the cyst and treatment of the residual cavity) or radical (including pericystectomy and anatomical liver resections).

• Pyogenic liver abscess represents a life-threatening bacterial infection of the liver. Surgical treatment is indicated in case of failure of conservative therapy (antibiotics combined or not with percutaneous drainage), which occurs mainly in multiloculated abscesses and those with biliary communications.

• Primary intrahepatic lithiasis (stones originated inside the intrahepatic biliary tree) is endemic in East Asia and much less common in the West. It is usually associated with intrahepatic biliary strictures and is responsible for recurrent episodes of cholangitis, hepatic atrophy, secondary biliary cirrhosis, and intrahepatic cholangiocarcinoma.

• Diagnosis of hepatolithiasis is usually established by non-invasive radiological methods. Accurate location of stones, detection of biliary strictures, identification of hepatic segments involved and/or atrophic, suspicion of cholangiocarcinoma, and/or the presence of cirrhosis and portal hypertension will ultimately lead the therapeutic approach.

• Treatment is challenging and sometimes controversial, and aims to prevent recurrent cholangitis and consequences of progression of disease (ultimately cholangiocarcinoma).

• Liver resection allows remotion of the stones, of the biliary strictures, and of the atrophic parenchyma, and ultimately diminishes the risk of cholangiocarcinoma. It seems to be the best surgical option for treatment of primary intrahepatic lithiasis.

• Well-established indications for hepatic resection of primary intrahepatic lithiasis include: i) lithiasis limited to one lobe, sector, or segment; ii) parenchymal hypo-atrophy; iii) presence of liver abscess; iv) failure of previous treatments; and v)suspected cholangiocarcinoma.

• Knowledge of hepatic segmentation is crucial for safe liver resection. Remnant liver parenchyma should have adequate vascular inflow, vascular outflow, and biliary drainage.

• Different methods of vascular control are available and useful to reduce bleeding during hepatectomy. Inflow occlusion is the easiest and best tolerated option. Total vascular exclusion of the liver is required in some cases of tumors close to the debouchment of the hepatic veins and inferior vena cava.

• The two main approaches to selective inflow hepatic control are intrafascial and extrafascial (or Glissonean). The first is required for tumors close to the hepatic hilum.

• Anterior approach, mainly using the hanging maneuver, seems to reduce blood loss, facilitates “no touch” resection, and reduces the risk of liver damage for mechanical compression of the remnant liver during surgery.

• Excessive intraoperative blood loss and the potential need for blood transfusion are major problems in hepatic resection for liver tumors.

• Decrease in blood loss is a goal in liver surgery, and several technical developments have been introduced for this purpose, such as the ultrasonic dissector, the water jet, the harmonic scalpel, the Ligasure®, and the tissue link dissecting sealer.

• Other advances in operative techniques have also contributed to reducing blood loss during liver transection: better determination of the liver transection plane with the use of intraoperative ultrasound, and better hepatic vein flow control (inflow and outflow) as well as strict central venous pressure control.This chapter aims to outline and overview the surgical techniques currently used in liver surgery.

• Segment-oriented anatomical hepatic resection has the advantages ofachieving tumor-free margin and preservation of sufficient functional liverparenchyma.

• In this context, hepatic resection can be performed based on the preciseanatomical location of the tumor, according to the segmental anatomy asdescribed by Couinaud.

• In the technical aspect, this approach offers the advantage of performingliver transection along avascular planes so as to minimize intraoperative bloodloss.

• Anatomical right liver resections include right hepatectomy (segments 5 to 8),right lobectomy (segments 4 to 8), right paramedian setorectomy (segments 5and 8), and right lateral sectorectomy (segments 6 and 7).

• Anatomical segment-oriented liver resections require accurate knowledge of landmarks and precise dissection of the hilar region. Appropriate surgical view, occasionally requiring associated laparotomy and thoracotomy, is crucial for a safe resection.

• Right liver mobilization (before or after parenchymal transection) is usually needed, and complete mobilization from the inferior vena cava is required if liver resection includes segment 1.

• After right hepatectomy or right lobectomy, fixation of the falciform ligament keeps the remnant liver in anatomical position and allows adequate outflow.

• An extrahepatic approach to vascular structures, combined with an intra-parenchymal left bile duct division, is the preferred technique to perform leftliver resection. IOUS is an indispensable resource – not only to confirm selective vascular disconnection, but also to identify the appropriate transection planeduring parenchyma transection.

• The left hepatic vascular pedicle is perpendicular in relation to the right pedicle when the round ligament is held upward during left hepatectomy.

• The transection plane of a left hepatectomy is initially vertical until the hilar plate, and becomes horizontal following the Arantius plane after the bile ductsection.

• A hanging maneuver is also a useful technique for left resection extended to segment 1 or to the middle hepatic vein, since the transection plane is the same as that for a right hepatectomy.

• Total vascular exclusion should be performed in case of voluminous tumors that are in close proximity to hepatic veins.

• Vascular control of the left middle hepatic trunk is achieved from the left to the right in a strict horizontal plane. Lowering segment 1 and cutting the Arantius ligament are mandatory in order to safely perform this vascular control.

• The laparoscopic liver resection procedure has evolved over the last two decades from a novel segmental operation to an established procedure with proven efficacy and safety in skilled hands.

• Adoption of laparoscopic liver resection has been variable among centers from 5-70% of resections. Throughout its evolution, numerous techniques and devices have been introduced into the field since the original description of pure laparoscopic approach. These innovations include stapler hepatectomy, hand-assist devices, single port access, and robotics.

• Laparoscopic liver resection was initially applied to the management of peripheral benign tumors and subsequently adapted for the routine management of malignant tumors. Multiple studies have subsequently confirmed the oncological non-inferiority of laparoscopic liver resection.

• Laparoscopic liver resection has been accepted as the standard of care for left lateral sectionectomy while major hepatectomy continues to evolve as a standard of care. Laparoscopic live donor hepatectomy and major robotic resections continue to be areas of investigation that have been recommended to proceed in the setting of a prospective study.

• The most important technical tools that have improved speed and safety of liver resection are: staplers, sealers, and ablation devices.

• Staplers now allow reliable and rapid closure of major blood vessels.

• Sealers allow secure transection of liver parenchyma, minimizing bleeding and securing small bile ducts.

• Ablation instruments allow a parenchymal sparing alternative to resection for deep, small tumors, and can be combined with simultaneous major liver resection to extend possibility of curative therapy.

• Patient and graft survival after liver transplantation (LT) has improved over time. Despite the options available to increase the donor pool, the expansion on indications for LT has surpassed the availability of grafts, exacerbating the scarcity of grafts.

• Clinical evaluation of potential recipients is crucial to avoid excessively early LT (with no benefit for patients with a good predicted survival without LT) but also excessively late LT (resulting in poorer outcomes). Timing and methods for organ allocation remain challenging.

• Partial liver grafts (including living-donor and splitted grafts) and marginal grafts represent options to increase the graft pool.

• Postoperative complications after LT remain significant and are mainly related to graft quality, recipient clinical status, immunosuppression, recurrence of hepatic disease, and technical aspects.

• LT in the setting of acute liver failure is uncommon and is accompanied by specific factors related to organ allocation and technical aspects.

• Results of liver transplantation (LT) for hepatic malignancies have been disappointing and mortality rates nearly prohibitive for benign tumors in initial trials.Clinical and surgical perioperative improvements show satisfactory outcomes in LT for end-stage chronic liver disease, and indications have increased. Currently, malignant and benign tumors are treated using LT; however, the scarcity of donors requires a selection of receptors whose could better profit of grafts.

• Liver transplantation should be considered the treatment of choice for selected patients with hepatocellular carcinoma (HCC) who are not candidates for surgical resection, and in whom malignancy is confined to the liver. Best results of LT for HCC are obtained in patients with a single tumor measuring less than 5 cm, or no more than three lesions measuring less than 3 cm each (Milan criteria).However, promising results have been achieved even when these classical criteria are extrapolated. LT for other malignancies primarily includes endocrine metastatic tumors. Cholangiocarcinoma and other malign tumors have controversial indications.

• Some benign tumors can represent indications for LT when other treatments, mostly partial hepatic resection, are not anticipated and symptoms or a risk of complication (rupture or malignization) are present.

• Although acute cellular and chronic rejection can lead to graft loss, early acute rejection has no impact on long-term graft function and recipient survival.

• Intensive immunosuppression is required in the first months after LT, when the risk of rejection is highest. A combination of immunosuppressive agents (most commonly a combination of steroids, a calcineurin inhibitor, and mycophenolate mofetil) is preferred to avoid high doses and collateral effects of each drug.

• Immunosuppression should be minimized after LT for hepatitis C related cirrhosis(due to the effect of increasing viral replication and progression of fibrosis) and for HCC, mainly in cases of recurrence (because immunosuppression accelerates tumor progression). Conversely, the level of immunosuppression should be higher after LT for autoimmune diseases.

• Long-term immunosuppression increases the risk of malignancies (skin tumors are the most frequent malignancies) and other collateral effects, such as nephrotoxicity (mainly related to calcineurin inhibitors), diabetes, neurotoxicity, and osteoporosis.

• The technical evolution and refinement of liver transplantation over the past 50 years has allowed liver replacement to alter the course of end-stage liver disease as a life-ending condition, thereby giving patients a second chance at a full and healthy life.

• The execution of donor hepatectomy, back-table preparation, recipient hepatectomy and graft implantation are all essential to the completion of a single liver transplant.

• Living donor liver transplantation needs to be carefully considered in select cases while preserving the well-being of the donor to the maximum extent possible.

• Early detection and management of vascular and biliary complications provides the best chance for a favorable outcome.