Hepatic surgery performed without a parenchyma-sparing policy carries relevant risks for patients’ survival due to the possible occurrence of postoperative liver failure for which its application is limited.(1) In particular, the coexistence of liver cirrhosis with hepatocellular carcinoma (HCC) has a considerable adverse effect on the surgical results: recent series are associated with mortality rates above 5%, which is significant,(2) and with resectability rates of 30–35%, which is relatively low.(3) For this reason, and with the increased use of ultrasound-guided percutaneous therapies,(4) surgical treatment of HCC is not necessarily the first-choice treatment and is now reserved for patients with normal bilirubin levels, no signs of portal hypertension and single small HCC.(5) By contrast, for colorectal cancer liver metastases (CLM), surgical treatment remains the gold-standard. The definition of resectability has shifted from a focus on tumour characteristics, such as number and size of tumours, to determination of whether both intra-hepatic and extra-hepatic disease can be completely resected, and whether such an approach is appropriate from an oncological standpoint. Therefore, the limitation of CLM surgery is whether it is technically feasible.(6.7) Progress with chemotherapy regimens has improved the resectability rate,(8) although surgery is still necessary in around 15–25% of patients.(9) By contrast, chemotherapy regimens have introduced new liver diseases that impair hepatic functional reserve and therefore increase the risk of postoperative liver failure, especially after removal of functioning parenchyma.(10) The main limiting factor for resectability is the need for major hepatectomy, which still represents a significant risk factor for perioperative mortality and morbidity.(11,12) Portal vein embolisation (PVE) has been devised with the double aim of increasing the safety of major liver resection and allowing more patients to benefit from surgical treatment.(13) However, liver failure – which affected 33% of patients who did not undergo PVE – still occurs in 10% of those who had the procedure.(14) With the growth of imaging techniques such as ultrasonography (US), alternative therapies such as percutaneous interstitial treatment have been devised for treating CLM as well as HCC.(15) Imaging techniques have also been introduced as aids for surgeons performing liver resection. Today, liver resections can be carried out with no mortality, even if associated with cirrhosis,(16,17) – this is achievable mainly because of intraoperative ultrasonography (IOUS). Indeed, ultrasound guidance, which allows the so-called ‘radical but conservative policy’,(18,19) offers an alternative to making major hepatectomy safer, as it reduces the need for major parenchymal removal.This policy has achieved resectability rates from outpatient evaluation of hepatectomy in approximately two-thirds of patients with HCC and CLM.(7,20)
The technical aspects of IOUS, its impact on liver surgery and its future applications – for both staging and resection guidance – are discussed below.
The use of IOUS in liver resection can be divided into three phases: liver exploration, planning of surgical strategy and guidance during the surgical procedures.
Most of the nodules detected by IOUS in the cirrhotic liver are not tumours: as a result, IOUS introduces a risk of overestimating tumour staging. Apart from those nodules with a mosaic ultrasonographic pattern, which are malignant in 84% of cases, only 24–30% of hypoechogenic (dark) nodules and 0–18% of hyperechogenic (bright) are neoplastic.(21,22) Even biopsy is an inadequate tool to overcome this problem. Therefore, differentiation of the lesions found at IOUS exploration is crucial. Further improvements in differential diagnosis of liver nodules with IOUS will be expected with the use of contrast agents(23); in particular those with a hepato-specific phase, which allow enhanced visibility for several minutes to hours after injection and give a panoramic view that can increase the detection of HCC.
Improving detection is the main target of contrast-enhanced IOUS (CEIOUS) in CLM. It is particularly useful for patients who undergo surgery after chemotherapy and whose liver nodules are not very visible with IOUS alone. CEIOUS gives better nodule visibility and detects 9% more adjunctive nodules compared with IOUS.(24) Therefore, CEIOUS increases sensitivity and should always be used in patients with CLM. It is even more useful when the lesions appear similar to the surrounding parenchyma: in these patients, the rate of missed disease is higher and, as a consequence, prognosis could be worse.(25) By contrast, when the lesions are darker than the surrounding liver parenchyma, the need for contrast-enhanced images decreases, for example, a bright liver with IOUS(26) that correlates with the degree of fatty change.In these circumstances, the visibility of CLM – which is generally hypoechogenic – is enhanced by the brightness of the surrounding liver parenchyma that mimics the effect of the contrast enhancement. As confirmation, we did not find any new sites with CEIOUS in those patients with a bright liver at IOUS. Using hepato-specific contrast agents that allow prolonged exploration could also benefit exploration of CLM.(27)
Planning of surgical strategy
Exploration of the liver with IOUS could have a great impact on surgical strategy but this depends on the background surgical policy. Indeed, if major hepatectomies are carried out in the minority of patients, even in extremely complex presentations,(7) just because of the extensive use of the IOUS-guidance, detection of new nodules is more suitable for changing the surgical strategy.
The relationship of the tumour and nearby hepatic vessels is important for planning the type of resection and, with this information, specific and tailor-made operations can be performed.(29,30) IOUS easily allows the surgeon to recognise whether a tumour is just in contact or invading the vessel wall, or is affecting proximal bile duct dilation. Depending on these features, it can be decided whether to resect the vessel and a precise surgical strategy can be defined. The main aim is to spare the major vessel even if it is in contact with the tumour and for that sparing the parenchyma fed by that vessel resulting in more conservative and otherwise unfeasible procedures. Further solutions are obtained by studying the venous drainage of the liver: the proven existence in most patients with a tumour that obstructs the venous drainage itself of communicating veins shunting the blood from an hepatic vein to another discloses many technical solutions to reduce the amount of parenchyma to be sacrificed and to increase the surgical feasibility.(19)
For most of the IOUS-guided parenchymal-sparing procedures described in this article, adequate incision and liver mobilisation is essential.
Anatomical resections – In HCC, it is necessary to perform anatomical resection with removal not only of the tumour and the surrounding liver parenchyma but also of the portal tree feeding the tumour.(30–32) However, the portal area, which delineates the segment or subsegment in which the tumour is located, cannot be seen on the liver surface without an interventional procedure.(28,33,34) Once the feeding portal branch has been identified with IOUS, it is compressed using the IOUS probe on one side of the liver and a finger on the opposite side: in this way it is possible to induce transient ischaemia of the portion of the liver distal to the compression site. The portion is marked using electrocautery, the compression is released and the resection can be carried out. This technique is simple, fast, not invasive and reversible: the possibility of modifying the compression site and the size of the resection means the extent of the resection can be adapted according to features of the tumour and the status of the surrounding liver.
Non-anatomical resections – For CLM, non-anatomical resection is commonly accepted as the correct approach ontologically.(35) For limited resections, IOUS-guidance plays a fundamental role: although there is no need to identify the area of the liver fed by the portal branch that is to be ligated, once the tumor is identified, the surgeon – using IOUS – can mark with electrocautery the border of the area to be removed on the surface of the liver. To carry out this manoeuvre, the flat, thin tip of the electrocautery probe is positioned between the probe and the liver surface, resulting in a shadow on the IOUS image that runs deeply just below the electrocautery border. Using this technique, the margin of the tumour can be lined up with the electrocautery border to ensure a safe edge for the incision. Another way to draw precisely on the liver surface with the aid of IOUS involves the fingertips. With the probe positioned on the liver surface, the surgeon’s fingertip pushes on the opposite side of the liver and its profile is visualised at IOUS; consequently, the distance between the fingertip and the tumour edge can be precisely estimated and the resection area marked on the liver surface.
Once the area to be resected has been drawn on the liver surface, the aim is to achieve a flat, regular cut surface.
Liver parenchyma dissection – The main advantage in using IOUS resection guidance is a modification of the traditional way of dissecting liver tissue, which was done on vertical planes to avoid tumour exposure on the cut surface. IOUS enables real-time visualisation of the dissection plane as it approaches the edge of the tumour and allows the direction to be modified if necessary; the dissection plane appears as an echogenic line because of entrapment of air bubbles and clots between the facing cut surfaces. This allows more conservative but radical treatments and a lower rate of major hepatectomies. It is essential to avoid accidental division of nearby vessels and, to this end, the so-called hooking technique has been devised.(36) When the vessel is exposed and skeletonised, it is encircled with a stitch, which is visualised by IOUS as an echogenic spot with a posterior shadow. Using sonographic control, the stitch, which is hooked over the exposed vessel, is gently pulled up, and the traction point is seen clearly. If the target site is correct, the portal branch is ligated and divided and resection is completed under IOUS guidance; conversely, if the exposed vessel was not the targeted one, it is spared and sacrifice of further liver parenchyma is avoided.
During liver dissection, backflow bleeding from the hepatic veins is an important source of blood loss and limiting this bleeding is a priority. An ultrasound-guided technique for control of backflow bleeding from the hepatic vein,(37) involves finger compression of the vein at its caval confluence, the position of which is confirmed by colour-flow analysis.
Post-resection control – IOUS offers two possibilities after nodule removal: one is the ‘water bath’ technique, which consists of real-time verification that the whole nodule has been removed in the resected liver specimen(38); the second is done by checking the cut surface refilled with saline.
US – and more recently CEIOUS – still remains the best method for staging. IOUS is certainly the best way for the surgeon to visualise liver anatomy and the association between tumors and intrahepatic vessels, which are crucial for planning liver resection. IOUS guarantees whenever possible both anatomical and limited resection with a radical intent. Resection procedures that are not IOUS guided can be dangerous or incomplete. IOUS has drastically reduced the rate of major hepatectomies in spite of complex presentations.(7,19,20) New ultrasound-guided operations have contributed to these results since they allow technical solutions that were previously not feasible.(29,39)
For all these reasons, IOUS should be in the armoury of hepatic surgeons and the challenge is to train young surgeons in ultrasound during their surgical education.
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