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Liver Resection and Laser Hyperthermia
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LASERS IN GENERAL SURGERY
+
.20
LIVER RESECTION AND LASER HYPERTHERMIA Philip
o.
Schneider, MO, PhD
The vascular nature of the liver and its predilection to bleed after injury or during the treatment of primary and metastatic tumors have naturally focused researchers and clinicians on methods to control hepatic bleeding. Excessive bleeding at the time of hepatic resection is associated with increased mortality and morbidity rates both at elective liver resection and in the emergency setting. One can argue that general advances in life support, intensive care, and blood banking have done much to improve the results of liver resection. Equally, it can be said, however, that a better understanding of liver anatomy and physiology has combined with certain technical advances to allow surgeons to achieve a degree of control during liver surgery that makes the operation safer. These technical advances include clinical laser applications and related techniques, which may facilitate resection with reduced blood loss and offer the prospect that clinicians may in the near future manage many hepatic tumors without resection. Liver surgery has the potential for degenerating into a terrifying exercise for the surgeon and anesthesiologist. Lest one be tempted by the availability of current advances in technical hardware to take too casual a view of these procedures, it should be stated that although lasers, ultrasonic dissectors, cryosurgery, argon beam coagulators, and other devices can greatly assist the surgeon with control of parenchymal bleeding and exposure of major vessels, they are minimally effective in the setting of disseminated intravascular coagulation and are of absolutely no assistance during most instances of major liver bleeding, which usually arise from hepatic veins, a portal vein improperly secured From the Division of Surgical Oncology, Department of Surgery, University of California Davis Cancer Center, Sacramento, California
SURGICAL CLINICS OF NORTH AMERICA VOLUME 72 • NUMBER 3 • JUNE 1992
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after division in the hilum, or injury to the vena cava at any site along its abutment with the liver. However, these modern devices do facilitate controlled resection with reduced blood loss compared with most fracture techniques. In addition, these technical advances and understanding of the results of liver resection have led to the development of ablative techniques-best termed "interstitial therapy"-which is in situ ablation of hepatic malignancies with either focal hyperthermia, cryosurgery, or ethanol injection. This overview discusses how the laser, the argon beam coagulator, and the ultrasonic dissector may be employed to reduce bleeding during hepatic surgery. Also, the role of the laser in the interstitial treatment of hepatic malignancies is reviewed in its context as one of several competing modalities for in situ management of hepatic tumors.
ANATOMY AND PHYSIOLOGY
Aside from the obvious need for surgeons to understand the anatomy of the major perihepatic vessels-the hepatic artery, portal vein, hepatic veins, and vena cava-an understanding of intrahepatic segmental anatomy is useful to the surgeon. 4 The size of the intrahepatic vessels at various sites indicates the likely ability of the surgeon to control bleeding with either the laser, the cautery, or such devices as the argon beam coagulator. 23, 29 The hepatic artery divides in the hilum to form two 3- to 5-mm diameter branches. Segmental hepatic artery branches are 1 to 2 mm in size. Arterioles within the periphery of the liver parenchyma generally are 25 f.Lm in diameter. The right and left portal vein range from 5 to 15 mm in diameter. Large distributing branches of the portal vein as much as 280 f.Lm in diameter are found at the level of the hepatic segments and successively branch to become portal venules averaging 35 f.Lm in the periphery of the hepatic lobule. The hepatic sinusoids are approximately 7.0 to 15 f.Lm in width. Terminal hepatic venules measure close to 45 f.Lm, and as tributaries coalesce, rapidly increase in size as the vessels approach the 8- to 20-mm hepatic veins proper in the posterior aspect of the liver. The periphery of the liver lobule, therefore, has vessels of small diameter amenable to coagulation by a variety of means and, if transected, likely to cease bleeding with pressure in the absence of extenuating circumstances. Segmental and sub segmental vessels of 1 to 2 mm are encountered as one proceeds centrally across the hepatic parenchyma. These larger vessels theoretically can be coagulated with laser photothermia but, in practice, frequently are not. In addition, within the portal triads are bile ducts, which can easily be cut by the cautery or laser but which cannot be sealed by these modalities. Aside from these specific vessel size constraints, the utility of various separate resection techniques can depend on the specific nature of the problem encountered. For example, enucleation of a peripherally
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located cavernous hemangioma would be expected to require a different resection technique than formal hepatic lobectomy or wedge resection. The clinical situation, of course, influences the technical approach dramatically, as is noted when comparing the multiply injured trauma patient with a liver injury with the patient undergoing elective hepatic resection. In the first case, ease of use and speed become important considerations for any technique to be acceptable. In addition to anatomy, physiologic factors that are difficult to define but can be termed "hepatic reserve" have a profound influence on the likelihood of bleeding. For example, hepatic resection in a child with neuroblastoma would be expected to be substantially different from hepatic resection in an adult with cirrhosis. However, in all circumstances, the goal is to reduce the morbidity and risk of death attendant on liver surgery by reducing blood loss. There is no physical technique that will allow single-pass transection of the liver with the sealing of all blood vessels and bile ducts. Initial hopes that electrocautery or laser thermal coagulation could provide a means to accomplish this have not been borne out.s Thus, a variety of techniques, both new and old, have focused on the differences in the elastic content of the vascular and biliary structures compared with hepatic parenchyma. By using such techniques, it is possible to manage parenchymal arteriolar and venular bleeding by isolating the larger blood vessels and occluding them prior to their division. I, 8, 10, 24 Thus, bleeding is prevented by identification of larger blood vessels before they are cut rather than by relying on radiofrequency or photothermal coagulation to cauterize vessels larger than 1 mm, a task these techniques cannot reliably perform. TECHNIQUE OF LIVER RESECTION
The techniques of hepatic resection and hepatic surgery have been detailed in numerous texts and articles. 8, 18,22,23 The key points emphasized here address parenchymal transection. As mentioned previously, control of perihepatic vessels is of the utmost importance, as these are the potential sources of significant rapid bleeding. In any technique of parenchymal transection, it is imperative that good visibility within the hepatic parenchyma be maintained once the transection has begun. Devices that incorporate as part of their design an aspiration feature, I, 10, 33, 38 plus additional suction units, can be employed to provide visibility of the biliary and vascular structures as the liver is transected. This very important virtue of suction alone has led to the development of a blunt "suction knife," which some surgeons find useful as a refinement of blunt fracture techniques. lo Parenchymal Transection
There have been two general schools of thought regarding parenchymal transection. 8 Knife-handle and finger fracture techniques have
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evolved from the idea that rapid parenchymal transection is essential to minimize bleeding by rapid removal of the specimen to allow packing and suturing of the transected hepatic surface. The alternative approach, afforded by newer methods of parenchymal transection such as ultrasonic cavitation and blunt dissection suction devices mentioned above, involves slow transection with good visibility of intrahepatic biliary and vascular structures. With either of these parenchymal transection techniques, the Pringle maneuver, various hepatic clamps such as the Storm or Lin clamp, or the hepatic "strap"3, 7, 18,27 can provide additional means for controlling bleeding as transection is accomplished. In this setting, one can proceed to divide the liver by rapid finger fracture or knife-handle or suction-knife dissection. Similarly, with such vascular control, transection with the ultrasonic dissector allows exposure of larger (> 1-mm) structures that can be divided prior to injury, ensuring control of bleeding and the avoidance of bile leaksY' 13, 25, 38 General Techniques
Ultrasonic Dissector-Cavitating Ultrasonic Surgical Aspirator (CUSA)
Surgeons have found the CUSA device to assist greatly with liver hemostasis. The device is a hollow titanium probe that oscillates longitudinally over a distance of 100 /-Lm at a frequency of 23 kHz. The field is kept dry by virtue of the aspiration feature and additional surgical aspirators, and the instrument is moved slowly. It causes small peripheral parenchymal vessels to be coagulated; the larger elastic-containing structures are isolated to be divided with clips or sutures.8, 12, 23 Argon Beam Coagula tor
Coupling of the radiofrequency electro surgical generator with coaxial argon gas flow allows electric current to arc via the gas to nearby tissue to achieve focal coagulation necrosis to a depth of approximately 2.4 mm.14 The gas flow, which can be as rapid as 12 Llminute, is usually operated in the 2 to 7 Llminute range and clears blood and debris away from the arc. By reducing local oxygen with the argon, the technique decreases the amount of surface eschar and carbonization compared with electrosurgery using the standard blade or ball tip.9 However, concerns have been raised that the gas flow and pressure have the potential to spread tumor,19 and there is also the possibility of air embolus, as argon under pressure might unintentionally be injected into hepatic veins. Thus far, these concerns have been more theoretical than verified. It is clear that there is a role for the argon beam device for coagulation of small vessels, analogous to that achieved by cavitating ultrasonic dissection.
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Dissection in the hilum in preparation for resection or during biliary surgery is facilitated by the argon beam coagulator. Troublesome small portal venous tributaries along the bile duct or within hilar areolar tissue are simply and rapidly controlled. Several companies, including Beacon, Valley Labs, and Birtcher, are expanding the utility of these instruments by combining standard electrosurgery units with the argon beam coagula tor. Control at the handpiece achieves a highly versatile instrument capable of coagulating with or without gas flow. Laser-assisted Resection
The CO 2 laser and the neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers have been extensively discussed in the setting of hepatic resection. 5, 17, 18 In the case of the latter, contact tips have extended the usefulness of the cutting characteristics of the laser .15,32,34 Unlike the bare Nd:YAG fiber, the tips provide the feeling of direct tissue contact, which many surgeons find more comfortable. A combination of Nd:YAG and CO 2 lasers in a single unit has been said to achieve a better combination of light frequencies for coagulation and vaporization. 18 The depth of tissue injury by the Nd:YAG laser is approximately 4.0 mm with temperatures as high as 200°C at the site of the contact. 5 With a decrease in hepatic blood flow, which can be achieved with clamping of the hepatic inflow with strapping or with Storm and Lin clamps, the width of the necrotic zone can be increased to 7 or 8 mm. 18 With the clear contact sapphire tip, a very small (2-mm) zone of necrosis occurs. By utilizing frosted tips, a broader zone of necrosis is possible with facilitation of resection through fibrotic liver. 17, 33, 38 This contact laser has a significant advantage over the ultrasonic dissector, which can be nearly useless in a fibrotic liver. The disadvantage of the laser technique is that, as with electrocautery or the cold surgical knife, discrimination of parenchyma from vascular and biliary structures is not possible. With larger vessels in the 2-mm range, cutting without coagulation occurs, thereby increasing blood 10ss.5 Recently, there have been several studies comparing the various techniques of hepatic resection in terms of rapidity of performance of a defined surgical procedure and the success of controlling bleeding. 32, 33, 38 In 1986, Tranberg et al reported, in a comparison of the Nd:YAG laser, the ultrasonic aspirator, and blunt dissection, that there was less tissue damage with the CUSA than with the other two techniques. 38 Extending their work, this group reported in 1987 on utilizing a frosted contact tip with the Nd:YAG laser at 15 W, and continuous duration in a similar comparison. 33 There appeared to be little difference in the blood loss produced with the contact laser and the ultrasonic dissector or the suction knife. Further work by Schroder et al in 1987 indicated that the noncontact laser may cause more extensive tissue damage and is not as good as the contact laser at achieving hemostasis. 32
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Summary
Surgeons who "grew up" in the era of rapid parenchymal transection using finger fracture or blunt techniques frequently find the newer CUSA and lasers somewhat slow. For these surgeons, it is likely that the argon beam coagulator in conjunction with their usual techniques for parenchymal fracture will meet their needs for speed and hemostasis. For those familiar with CUSA and the laser, the fibrotic liver, once a barrier to effective dissection with the CUSA, can be overcome with blunt dissection techniques or the contact laser. One must bear in mind the theoretical risk of air embolus with the argon beam coagulator or free fiber laser with coaxial gas flow, particularly when working posteriorly near larger hepatic venous tributaries and with relatively high gas flows. Table 1 provides a qualitative comparison of the various techniques used for parenchymal transection. It is important to emphasize once again that the newer technology does not necessarily solve the significant bleeding problems that can develop during hepatic resection. It can be a humbling experience to resect larger tumors that decrease hepatic pliability, or to perform hepatectomy in patients with prior right adrenal or right renal surgery, or to resect tumors that are posteriorly located near the inferior vena cava or hepatic veins. In these instances, the standard vascular surgery techniques of proximal and distal control and careful suturing frequently will be of more value than the technical advances discussed.
INTERSTITIAL THERAPY OR IN SITU ABLATION OF INTRAHEPATIC MALIGNANCIES
For many reasons, patients with intrahepatic malignancies may not be suitable candidates for resection. Systemic metastatic disease and Table 1. QUALITATIVE COMPARISON OF HEPATIC PARENCHYMAL TRANSECTION TECHNIQUES WITHOUT VASCULAR OCCLUSION Visibility of Vascular/Biliary Structures Blunt fracture Blunt fracture & suction Blunt fracture & argon beam coagulator CUSA & suction CUSA & argon beam coagulatQr Contact laser photocoagulation *+ + + +
=
most;
+
=
least.
Rapidity of Performance
Blood Loss*
Cost*
Poor Fair Fair
Rapid Rapid Rapid
++++ ++++ +++
+ + ++
Good Very good
Slow Slow
++ +
+++ ++++
Fair
Intermediate
+++
+++
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intra-abdominal disease outside the liver account for the bulk of the contraindications. While it appears that resection of as many as three or four lesions in the liver may be associated with longevity in the setting of metastatic colorectal cancer,15 the location of one or two lesions within the liver may be such that resection is not possible. In addition, frequently, there are patients with medical illnesses that make them unsuitable for major liver resection. In recent years, it has also become apparent that patients with metastatic neuroendocrine tumors, such as carcinoid and gastrinoma, may achieve substantial symptomatic benefit by the ablation of hepatic metastases even when the primary or every metastatic site is not ablated. Investigators have searched for a means to treat liver lesions in situ in such a fashion that the disease is controlled and the complications minimized. Impetus has been given to the possible role of in situ tumor treatment by accumulated evidence, summarized in the data from the Hepatic Tumor Registry, that the expected benefits of resection apply also to patients who have surgical margins as close as 1 em around the metastatic lesion. 15, 16 The same type of information about margins is not available for primary hepatocellular carcinoma. However, there is extensive evidence for the palliative benefit of localized resection in these hepatoma patients, who are frequently not candidates for major liver resection because of extensive cirrhosis coincident with their cancer. Thus, the goal of effective in situ treatment with margins that might allow a cure has been pursued by several investigators (Fig. 1). Techniques for the interstitial treatment of these hepatic tumors include alcohol injection, cryosurgery, laser ablation, laser hyperthermia, electrodesiccation, and interstitial radiation implantation. In order to understand the place of laser hyperthermia in this treatment armamentarium, these methods will be briefly discussed. First, it is useful to consider a technique for selective photovaporization of liver tumors. Although not a resection technique, it is an in situ attempt to ablate individual liver lesions, and it is based on the premise that a cure is a very real goal of in situ techniques if one can achieve a proper margin.
Selective Photovaporization of Liver Tumors
The liver is mobilized to obtain exposure and allow access to the lesion in question. The liver capsule is scored with the electrocautery or the laser in a circular fashion directly over the lesion (Fig. IA). This is the base of a cone of dissection: the apex of the cone is the metastasis to be treated. A broad base is necessary for deeper and larger lesions. Parenchymal dissection is carried toward the lesion in a cone-like fashion to expose the lesion (Fig. IB). The relation of the lesion to the hepatic veins and portal tracts is carefully considered. Once the lesion has been exposed in this manner, one can vaporize it safely under direct vision (Fig. IC). An Nd:YAG laser with a bare fiber is used for this purpose. The laser power setting is approximately
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A
B Figure 1. Technique of selective photovaporization. A, Deep-seated hepatic metastases are approached by first scoring the liver capsule, thus creating the base of a cone of dissection. B, Dissection of the cone of hepatic parenchyma ends approximately 1 cm from the hepatic metastasis, which is the apex of the cone. Illustration continued on opposite page
80 W applied as a continuous beam, with the laser fiber being held 1 cm from the lesion being treated and applied until vaporization of the lesion occurs. A specialized smoke evacuator is necessary to remove the rather pungent laser plume. A 1- to loS-cm cuff of normal tissue is included in the field of vaporization to ensure adequate margins (Fig. 1D).
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c
D Figure 1 (Continued). C, Photoablation is accomplished with a bare-fiber Nd:YAG laser. 0, The goal of vaporization is to achieve a minimum of a 1-cm margin around each hepatic metastasis.
The appearance of the walls of the cavity is carefully noted, and any bleeding or bile leak is managed by suture ligation or repair. Particular attention must be directed to preservation of bile drainage of the remaining segments of the liver, as disruption of the biliary drainage of a substantial portion of the liver will ensure the development of a troublesome biliary fistula in the postoperative period. A closed, active drain is left for a few days to manage blood, lymph, and bile drainage.
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Hilar control without temporary occlusion or ligation of the hepatic blood supply will usually allow safe resection, especially if the CUSA is used to dissect to the point at which vaporization is initiated. The key to safe laser photoablation is adequate exposure of the entire metastasis during the vaporization. The broad-based cone provides clear visibility of the walls of the tumor site after ablation, so that damaged biliary and vascular structures can be repaired. While offering tumor ablation to a few patients unable to undergo resection, laser photoablation is technically time consuming and difficult. Direct vision to avoid bleeding requires a large dissection even to approach the lesion for vaporization. When considering these factors, the following interstitial therapies appear more promising. General Comments Regarding Interstitial Techniques
The use of interstitial or in situ therapies has been driven by the fact that most patients who undergo liver resection for either metastatic disease or hepatocellular carcinoma will ultimately succumb to their cancer. If a relatively safe means could be employed to ablate lesions and possibly cure the few patients who are curable and, at the same time, reduce the morbidity and mortality rates of the therapy, most such patients would be better served. Improved hepatic imaging, in particular the development of realtime ultrasound, has enabled radiologists to visualize lesions in the range of 2.0 cm rather easily percutaneously. Employing intraoperative ultrasound, resolution can be further improved. Ultrasound is useful both for identifying the site of a metastasis and for placing an interstitial treatment modality into the tumor site. Ultrasound aids in defining the margins of the tumor site and can be used to monitor the ongoing effects of tissue damage such as thermal or freeze injury. The tracking of alcohol into the liver interstitium after ethanol injection can also be monitored with ultrasound. Follow-up analysis by CT, MR imaging, or ultrasound can then be employed as an absolute anatomic indicator of treatment effectiveness. The use of tumor markers such as carcinoembryonic antigen, alpha-fetoprotein, or neuroendocrine secretory products can also be used as an indirect means of assessing the efficacy of treatment, although radiologic imaging is the preferred method for assessing the response to therapy. Description of Treatments Cryotherapy
In 1987, Ravikumar et al reported their experience with hepatic cryosurgery for disease from colon cancer metastatic to the liver. 31 Despite the use of cryosurgery to treat a variety of neoplasms at various body sites, it was only with improvement in technology and the ability
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to use an 8- and 12-mm liquid nitrogen-cooled probe that could be placed interstitially at surgery that the treatment could be delivered effectively to deep sites. Verification of the effectiveness of therapy could be obtained anatomically by using real-time ultrasound to measure the size of the growing ice ball caused by freezing. Freezing and thawing for three cycles was an effective means of ensuring tumor necrosis. 28, 30 The general size of the lesions treated by this group was less than 3.0 cm. Zhou et aI, in the following year, reported an experience using cryosurgery with hepatocellular carcinoma. 39 Sixty patients were treated using surface freezing with hemispherical areas of necrosis of 9 cm diameter with a 6-cm probe or 6-cm areas of necrosis with a 3-cm probe obtained by placing the freezing plate onto the surface of the liver. Survival appeared to be improved in 27 cases treated with cryosurgery alone, with a 2-year survival rate of 23% and a 5-year survival rate of 4%, although this represents a select group of patients. Three papers report a total of 35 patients forming the bulk of current registered cryotherapy experience with metastatic disease. 28, 30, 31 Smaller lesions «4.0 cm) appear to respond well, and survival data from uncontrolled series appear promising. The disadvantage of cryotherapy appears to be that it requires an operation in order to place the large probes near the lesions. Thus, the morbidity of a surgical procedure must be factored into the analysis of morbidity and mortality rates. The treatment has generally been safe, with no frequent treatment-associated complications having been recorded. Air embolus can occur with the technique of interstitial treatment via the tract of the dilator required to place the cryoprobes, and an unusual nitrogen embolus has been described. 25, 28 Bleeding after freeze-thaw "cracking" of the liver and myoglobulinuria have been reported in isolated instances. 25, 28, 30 Vessels tolerate cooling well, but bile duct stricture or occlusion occurs readily. Alcohol Injection
There is a rising tide in enthusiasm for percutaneous introduction of absolute ethanol into lesions by a fine needle utilizing ultrasonic guidance. With ethanol injection, extensively reported on by Livraghi and Shiina and their coworkers, complications were rare except for occasional pain associated with extravasation of alcohol into the peritoneal cavity. 20-22, 36 Systemic alcohol injection is unlikely to occur. The difficulty with embracing the concept of alcohol therapy enthusiastically is the well-established fact that when alcohol is administered, its distribution is not geometrically predictable. 25 The material tracks along tissue planes of least resistance and, in particular, misses areas of tumor characteristically fibrotic or encased in the fibrotic liver. Metastatic lesions in particular are prone to incomplete destruction. 21 In addition, whereas the distribution of the alcohol can be tracked ultrasonically, the biologic effect-that is, tumor necrosis-cannot be monitored by ultrasonic guidance until actual tumor necrosis has occurred, as confirmed by follow-up studies 2 or more weeks after
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treatment. Additionally, the problem of being unaware of the extent of biologic effectiveness creates problems in planning treatment and identifying areas for injection and the volume of alcohol to be injected so that larger lesions can be treated. 25 However, the general consensus is that survival rates are quite acceptable in that the treatments may be performed two, three, or more times to create effective necrosis of a given tumor. In fact, repeated treatments are probably mandatory in view of the difficulty in predicting how much alcohol is required to infarct a given tumor mass. It is generally agreed that lesions smaller than 3 cm are the most amenable to this treatment, although it should be emphasized that relatively few patients have been studied. The four largest experiences 2o, 21, 35, 36 total 225 cases (211 cases of hepatoma, 14 cases of metastatic disease), although there are many smaller series reported in abstract form discussing this evolving technology. The chief advantages are low cost, ease of administration, and low toxicity. Combination with transcatheter embolization may extend the utility of the technique. Interstitial Radiotherapy
Little information exists about interstitial or brachytherapy of intrahepatic malignancies despite the known utility of the technique for tumors close to the body surfaces and employment at laparotomy for advanced disease. The two methods-implantation of the tumor with radioactive sources or employment of afterloading catheters that can be used to guide radiation source placement-have benefited from technical advances in computer planning, stereotactic guidance of catheter placement, and high-speed computerized source placement via afterloading catheters. However, treatment of liver tumors reported thus far has relied on ultrasound-guided placement of catheters or radioactive sources in only a few patients. 6 The effects of therapy can only be monitored over time with follow-up imaging. Interstitial Laser Hyperthermia
Clinically, Hashimoto et aI, in 1985,13 were the first to apply the concept of interstitial thermal injury utilizing laser light. They recognized that light administered by the Nd:YAG laser could deliver energy at the tip of a transmission fiber placed interstitially. Previous experimental work by others had established that the injury is a spherical lesion at the tip of the fiber, which, as with the modalities discussed above, can be followed using real-time ultrasound. Since this report, others, including Hahl et aI, established that the technique can be safe; and, as with percutaneous ethanol injection, the laser fibers can be inserted via percutaneously placed 14-gauge needles introduced under ultrasonic guidance. l l The extent of the thermal injury is determined, as in all laser techniques, by the power in watts and the exposure time as well as by
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the characteristics of the light wavelength and intensity and the absorption characteristics of the tissue. In general, using. the Nd:YAG laser, the power applied has ranged from 0.5 W to 6.0 W. Exposure times have ranged from 500 to 1000 seconds. An advantage within the liver (especially with tumors located near major vascular structures one wishes to preserve) is the thermal protection afforded by blood flow, which will save major vessels from injury. Therefore, the technique has potential application for lesions near structures that will make them surgically unresectable. 25 However, heat does have the potential for causing bile duct injury leading to obstruction or narrowing. An additional danger is related to the power setting, as has been reported by Schroder and associates. With the Nd:YAG laser at low power settings, in the range of 0.5 to 1.5 W, no cooling is needed. However, if 4 to 6 W of power is applied to decrease the exposure time, most investigators have used coaxial gas flow in the range of 1 LI minute to provide cooling. The application of heat and gas under pressure in a closed space has led to a fatal air embolism. 33 It does appear that the lower power settings will at least have the advantage of diminishing the risk of embolus, as gas cooling is not required. The tiijle required for creating therapeutic heat injury will be longer, however. To ensure total ablation of larger lesions, one must carefully place a pattern of fibers such that the entire tumor is encompassed. A spread or pattern of laser fibers can achieve this effect. The principal advantage of this technique is that the extent of the necrosis can be monitored with real-time ultrasound and adjusted at the time of treatment. Also, the injury is predictably spherical, unlike the irregular lesions resulting from alcohol injection. 2 Radiofrequency Electrodesiccation
In 1990, McGahan et al published their experience utilizing a standard electro surgical generator to apply radiofrequency energy in an interstitial fashion via a percutaneously introduced fine needle sheathed in nonconductive plastic. 26 The bare 1.0-cm tip was placed with ultrasonic guidance in the desired area of treatment. During the power application and monitoring of the effect with real-time ultrasound, spherical defects are created with diameters directly correlated with the power applied from the electrosurgical generator. This remains an experimental technique but is being performed in the clinical research setting and may prove ultimately to be an inexpensive and efficacious way to treat hepatic tumors. Complications
The introduction of probes into the interstitium and large areas of resulting necrosis may predispose to infection. With a variety of
~ a.
Table 2. COMPARISON OF TECHNIQUES FOR IN SITU HEPATIC TUMOR ABLATION*
Criterion Ease of application Precision and predictability Ease of real·time monitoring Accessibility of ail liver Treatment frequency Ease of retreatment Equipment expense Hospitalization time Staff required
• + ++ + +
Percutaneous Alcohol Injection
Percutaneous Laser Hyperthermia
++ + + ++ +
+ ++++ ++++ +++++ ++++ + +++ +
+++++ +++ ++ ++++ ++ ++++ +++++ +++++
++++ ++++ ++++ ++++ +++ ++++ + ++++
Surgeon anesthesiologist, OR staff
Surgeon anesthesiologist, OR staff
interventional radiologist
interventionai radiologist
Laser Vaporization
+ ++++ Direct vision
= greatest advantage.
Cryotherapy
Percutaneous Interstitial Radiotherapy
++ +++
Percutaneous Radiofrequency Electrodesiccation
+++ ++++ +++
++++ ++++ ++++ ++++ +++ ++++ +++ ++++
Interventional radiologist, physicist, radiation therapist
Interventional radiologist, possibly anesthesiologist
Not possible
++++ Unknown
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transcatheter embolization techniques, larger tumors that become necrotic have increased rates of infection. Thus, antibiotic prophylaxis and monitoring for infection are required in any of these patients receiving interstitial therapies. Although complications appear to be surprisingly few in the short term and the discomforts of the procedures are well tolerated by most patients, the potential for biliary toxicity from heat or alcohol with stricturing and bile duct occlusion must be considered. In addition, with thermal techniques, although it is established that healing of the areas occurs by contraction and fibrosis, one must be alert to the possibility and long-term risk of hemobilia. Summary
Table 2 provides a comparison of these interstitial and in situ techniques, assessing several criteria and utilizing and expanding on an excellent review by Masters et al. 25 The rapid advance of technology and cross-fertilization between groups using different interstitial techniques will lead to a clear understanding of the benefits and limits of each. However, there is essentially no information at the present time to suggest that these techniques should be used in lieu of hepatic resection in an attempt to cure patients who are good operative risks. There are insufficient data of a controlled nature to determine that there has been a survival or palliative benefit in many of the patients so treated. Nevertheless, as it is clear that these treatments cause tissue destruction in an appropriate nonmorbid way and that they are well tolerated with low risk to the patients, it is entirely conceivable that interstitial techniques will replace hepatic resection in some instances in the future, particularly for lesions smaller than 3 cm. References 1. Baer HU, Maddem GI, Blumgart LH: New water-jet dissector: Initial experience in hepatic surgery. Br J Surg 78:502-503, 1991
2. Bosman S, Phoa SSK, Mosma A, et al: Effect of percutaneous interstitial thermal laser on normal liver of pigs: Sonographic and histopathologic correlations. Br J Surg 78:572-575, 1991
3. Brown DA, Pommier M, Woltering EA, et al: Nonanatomic hepatic resection for secondary hepatic tumors with special reference to hemostatic technique. Arch Surg 123:2063-2066, 1980
4. Campra JL, Reynolds TB: The hepatic circulation. In Arias I, Popper H, Schacter 0, et al (eds): The Liver: Biology and Pathobiology. New York, Raven Press, 1982, pp 627-645
5. Dixon JA: General surgical applications of lasers. In Surgical Application of Lasers. Chicago, Year Book Medical Publishers, 1987, pp 119-143 6. Dritschilo A, Grant EG, Harter KW, et al: Interstitial radiation therapy for hepatic metastases: Sonographic guidance for applicator placement. AJR 146:275-278, 1986 7. Ebara M, Ohto M, Sugiura N, et al: Percutaneous ethanol injection for the treatment of small hepatocellular carcinomas: Study of 95 patients. Gastroenterology 5:616-626, 1990 8. Foster J: Liver resection techniques. Surg Clin North Am 69:1-250, 1989
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9. Goldberg SM, Gordon PH, Nivatvongs S: The basic application of electrosurgery. In Essentials of Anorectal Surgery. Philadelphia, JB Lippincott, 1980, pp 229-233 10. Haapiainen R, Schroder T: The suction knife in liver surgery. Am J Surg 157:340342, 1989 11. Hahl J, Haapiainen R, Ovaska J, et al: Laser-induced hyperthermia in the treatment of liver tumors. Lasers Surg Med 10:319-321, 1990 12. Hardy KJ, Martin J, Fletcher DR, et al: Hepatic resection: Value of operative ultrasound and ultrasonic dissection. Aust NZ J Surg 59:621-623, 1989 13. Hashimoto D, Takami M, Idezuki M: In depth radiation therapy by Nd:YAG laser for malignant tumors of the liver under ultrasonic imaging [abstract]. Gastroenterology 88:AI663, 1985 14. Hernandez AD, Smith JA, Jeppson KGB, et al: A controlled study of the argon beam coagulator for partial nephrectomy. J Urol 143:1062-1065, 1990 15. Hughes KS, Rosenstein RB, Songhorabodi S, et al: Resection of the liver for colorectal carcinoma metastases: A multi-institutional study of long-term survivors. Dis Colon Rectum 31:1-4, 1988 16. Hughes KS, Simon R, Songhorabodi S, et al: Resection of the liver for colorectal carcinoma metastases: A multi-institutional study of patterns of recurrence. Surgery 100:278-284, 1986 17. Joffe SN: Contact YAG laser system in abdominal surgery, in particular hepatic and pancreatic surgery. Semin Surg Oncol 5:48-56, 1989 18. Joffe SN: Liver resection. In Lasers in General Surgery. Baltimore, Williams & Wilkins, 1989, pp 100-124 19. Lanzifame RJ, Qiu K, Rogers DW, et al: Comparison of local tumor recurrence following excision with the CO, laser and argon beam coagulating laser. Lasers Surg Med 8:515-520, 1988 20. Livraghi T, Vettori C: Percutaneous ethanol injection therapy of hepatoma. Cardiovasc Intervent Radiol 13:146-152, 1990 21. Livraghi TG, Vettori C, Lazzaroni S: Liver metastases: Results of percutaneous ethanol injection in 14 patients. Radiology 179:709-712, 1991 22. Livraghi T, Festi D, Monti F, et al: US-guided percutaneous alcohol injection of small hepatic and abdominal tumors. Radiology 161:309-312, 1986 23. Longmire WD, Tompkins RK: Manual of Liver Surgery. New York, Springer-Verlag, 1981 24. Mason GR: Hepatic resection technique. Am J Surg 157:343-345, 1989 25. Masters A, Steger AC, Brown SG: Role of interstitial therapy in the treatment of liver cancer. Br J Surg 78:5189-523, 1991 26. McGahan JP, Browning JP, Brock JM, et al: Hepatic ablation using radiofrequency electrocautery. Invest Radiol 25:267-270, 1990 27. Mies S, Raia S: A simple method for controlling hemorrhage during hepatectomy. Surg Gynecol Obstet 168:265-266, 1989 28. Onik G, Rubinsky B, et al: Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon carcinoma: Preliminary results. Cancer 67:901-907, 1991 29. Rappaport AM: Physioanatomic considerations. In Schiff L, Schiff ER (eds): Diseases of the Liver. Philadelphia, JB Lippincott, 1982, pp 1-57 30. Ravikumar TS, Steele GD: Hepatic cryosurgery. Surg Clin North Am 69:433-440, 1989 31. Ravikumar TS, Kane R, Cady B, et al: Hepatic cryosurgery with intraoperative ultrasound monitoring for metastatic colon carcinoma. Arch Surg 122:403-409, 1987 32. Schroder T, Brackett K, Joffe SN: An experimental study of the effects of electrocautery and various lasers on gastrointestinal tissue. Surgery 101:691-697, 1987 33. Schroder T, Hasselgren P-O, Brackett K, et al: Techniques of liver resection: Comparison of suction knife, ultrasonic dissector, and contact Nd:YAG laser. Arch Surg 122:1166-1171, 1987 34. Schroder TM, Puolakkainen PA, Hahl J, et al: Fatal air embolism as a complication of laser-induced hyperthermia. Lasers Surg Med 9:183-185, 1989 35. Sheu Jc, Sung JL, Huang GT, et al: Intratumor injection of absolute ethanol under ultrasound guidance for the treatment of hepatocellular carcinoma. Hepatogastroenterology 34:255-261, 1987
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36. Shiina 5, Tagawa K, Unuma T, et al: Percutaneous ethanol injection therapy of hepatocellular carcinoma: Analysis of 77 patients. AJR 155:1221-1226, 1990 37. Tanaka K, Okazaki H, Nakamura S, et a1: Hepatocellular carcinoma: Treatment with a combination therapy of transcatheter arterial embolization and percutaneous ethanol injection. Radiology 179:713-717, 1991 38. Tranberg KG, Rigotti P, Brackett KA, et al: Liver resection: A comparison using the Nd:YAG laser, an ultrasonic surgical aspirator, or blunt dissection. Am J Surg 151:368373,1986 39. Zhou X-D, Tang ZY, Yu YQ, et al: Clinical evaluation of cryosurgery in the treatment of primary liver cancer. Cancer 61:1889-1892, 1988
Address reprint requests to Philip D. Schneider, MD, PhD The University of California Davis Cancer Center Division of Surgical Oncology Department of Surgery 4501 X Street Sacramento, CA 95817
LASERS IN GENERAL SURGERY
+
.20
LIVER RESECTION AND LASER HYPERTHERMIA Philip
o.
Schneider, MO, PhD
The vascular nature of the liver and its predilection to bleed after injury or during the treatment of primary and metastatic tumors have naturally focused researchers and clinicians on methods to control hepatic bleeding. Excessive bleeding at the time of hepatic resection is associated with increased mortality and morbidity rates both at elective liver resection and in the emergency setting. One can argue that general advances in life support, intensive care, and blood banking have done much to improve the results of liver resection. Equally, it can be said, however, that a better understanding of liver anatomy and physiology has combined with certain technical advances to allow surgeons to achieve a degree of control during liver surgery that makes the operation safer. These technical advances include clinical laser applications and related techniques, which may facilitate resection with reduced blood loss and offer the prospect that clinicians may in the near future manage many hepatic tumors without resection. Liver surgery has the potential for degenerating into a terrifying exercise for the surgeon and anesthesiologist. Lest one be tempted by the availability of current advances in technical hardware to take too casual a view of these procedures, it should be stated that although lasers, ultrasonic dissectors, cryosurgery, argon beam coagulators, and other devices can greatly assist the surgeon with control of parenchymal bleeding and exposure of major vessels, they are minimally effective in the setting of disseminated intravascular coagulation and are of absolutely no assistance during most instances of major liver bleeding, which usually arise from hepatic veins, a portal vein improperly secured From the Division of Surgical Oncology, Department of Surgery, University of California Davis Cancer Center, Sacramento, California
SURGICAL CLINICS OF NORTH AMERICA VOLUME 72 • NUMBER 3 • JUNE 1992
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after division in the hilum, or injury to the vena cava at any site along its abutment with the liver. However, these modern devices do facilitate controlled resection with reduced blood loss compared with most fracture techniques. In addition, these technical advances and understanding of the results of liver resection have led to the development of ablative techniques-best termed "interstitial therapy"-which is in situ ablation of hepatic malignancies with either focal hyperthermia, cryosurgery, or ethanol injection. This overview discusses how the laser, the argon beam coagulator, and the ultrasonic dissector may be employed to reduce bleeding during hepatic surgery. Also, the role of the laser in the interstitial treatment of hepatic malignancies is reviewed in its context as one of several competing modalities for in situ management of hepatic tumors.
ANATOMY AND PHYSIOLOGY
Aside from the obvious need for surgeons to understand the anatomy of the major perihepatic vessels-the hepatic artery, portal vein, hepatic veins, and vena cava-an understanding of intrahepatic segmental anatomy is useful to the surgeon. 4 The size of the intrahepatic vessels at various sites indicates the likely ability of the surgeon to control bleeding with either the laser, the cautery, or such devices as the argon beam coagulator. 23, 29 The hepatic artery divides in the hilum to form two 3- to 5-mm diameter branches. Segmental hepatic artery branches are 1 to 2 mm in size. Arterioles within the periphery of the liver parenchyma generally are 25 f.Lm in diameter. The right and left portal vein range from 5 to 15 mm in diameter. Large distributing branches of the portal vein as much as 280 f.Lm in diameter are found at the level of the hepatic segments and successively branch to become portal venules averaging 35 f.Lm in the periphery of the hepatic lobule. The hepatic sinusoids are approximately 7.0 to 15 f.Lm in width. Terminal hepatic venules measure close to 45 f.Lm, and as tributaries coalesce, rapidly increase in size as the vessels approach the 8- to 20-mm hepatic veins proper in the posterior aspect of the liver. The periphery of the liver lobule, therefore, has vessels of small diameter amenable to coagulation by a variety of means and, if transected, likely to cease bleeding with pressure in the absence of extenuating circumstances. Segmental and sub segmental vessels of 1 to 2 mm are encountered as one proceeds centrally across the hepatic parenchyma. These larger vessels theoretically can be coagulated with laser photothermia but, in practice, frequently are not. In addition, within the portal triads are bile ducts, which can easily be cut by the cautery or laser but which cannot be sealed by these modalities. Aside from these specific vessel size constraints, the utility of various separate resection techniques can depend on the specific nature of the problem encountered. For example, enucleation of a peripherally
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located cavernous hemangioma would be expected to require a different resection technique than formal hepatic lobectomy or wedge resection. The clinical situation, of course, influences the technical approach dramatically, as is noted when comparing the multiply injured trauma patient with a liver injury with the patient undergoing elective hepatic resection. In the first case, ease of use and speed become important considerations for any technique to be acceptable. In addition to anatomy, physiologic factors that are difficult to define but can be termed "hepatic reserve" have a profound influence on the likelihood of bleeding. For example, hepatic resection in a child with neuroblastoma would be expected to be substantially different from hepatic resection in an adult with cirrhosis. However, in all circumstances, the goal is to reduce the morbidity and risk of death attendant on liver surgery by reducing blood loss. There is no physical technique that will allow single-pass transection of the liver with the sealing of all blood vessels and bile ducts. Initial hopes that electrocautery or laser thermal coagulation could provide a means to accomplish this have not been borne out.s Thus, a variety of techniques, both new and old, have focused on the differences in the elastic content of the vascular and biliary structures compared with hepatic parenchyma. By using such techniques, it is possible to manage parenchymal arteriolar and venular bleeding by isolating the larger blood vessels and occluding them prior to their division. I, 8, 10, 24 Thus, bleeding is prevented by identification of larger blood vessels before they are cut rather than by relying on radiofrequency or photothermal coagulation to cauterize vessels larger than 1 mm, a task these techniques cannot reliably perform. TECHNIQUE OF LIVER RESECTION
The techniques of hepatic resection and hepatic surgery have been detailed in numerous texts and articles. 8, 18,22,23 The key points emphasized here address parenchymal transection. As mentioned previously, control of perihepatic vessels is of the utmost importance, as these are the potential sources of significant rapid bleeding. In any technique of parenchymal transection, it is imperative that good visibility within the hepatic parenchyma be maintained once the transection has begun. Devices that incorporate as part of their design an aspiration feature, I, 10, 33, 38 plus additional suction units, can be employed to provide visibility of the biliary and vascular structures as the liver is transected. This very important virtue of suction alone has led to the development of a blunt "suction knife," which some surgeons find useful as a refinement of blunt fracture techniques. lo Parenchymal Transection
There have been two general schools of thought regarding parenchymal transection. 8 Knife-handle and finger fracture techniques have
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evolved from the idea that rapid parenchymal transection is essential to minimize bleeding by rapid removal of the specimen to allow packing and suturing of the transected hepatic surface. The alternative approach, afforded by newer methods of parenchymal transection such as ultrasonic cavitation and blunt dissection suction devices mentioned above, involves slow transection with good visibility of intrahepatic biliary and vascular structures. With either of these parenchymal transection techniques, the Pringle maneuver, various hepatic clamps such as the Storm or Lin clamp, or the hepatic "strap"3, 7, 18,27 can provide additional means for controlling bleeding as transection is accomplished. In this setting, one can proceed to divide the liver by rapid finger fracture or knife-handle or suction-knife dissection. Similarly, with such vascular control, transection with the ultrasonic dissector allows exposure of larger (> 1-mm) structures that can be divided prior to injury, ensuring control of bleeding and the avoidance of bile leaksY' 13, 25, 38 General Techniques
Ultrasonic Dissector-Cavitating Ultrasonic Surgical Aspirator (CUSA)
Surgeons have found the CUSA device to assist greatly with liver hemostasis. The device is a hollow titanium probe that oscillates longitudinally over a distance of 100 /-Lm at a frequency of 23 kHz. The field is kept dry by virtue of the aspiration feature and additional surgical aspirators, and the instrument is moved slowly. It causes small peripheral parenchymal vessels to be coagulated; the larger elastic-containing structures are isolated to be divided with clips or sutures.8, 12, 23 Argon Beam Coagula tor
Coupling of the radiofrequency electro surgical generator with coaxial argon gas flow allows electric current to arc via the gas to nearby tissue to achieve focal coagulation necrosis to a depth of approximately 2.4 mm.14 The gas flow, which can be as rapid as 12 Llminute, is usually operated in the 2 to 7 Llminute range and clears blood and debris away from the arc. By reducing local oxygen with the argon, the technique decreases the amount of surface eschar and carbonization compared with electrosurgery using the standard blade or ball tip.9 However, concerns have been raised that the gas flow and pressure have the potential to spread tumor,19 and there is also the possibility of air embolus, as argon under pressure might unintentionally be injected into hepatic veins. Thus far, these concerns have been more theoretical than verified. It is clear that there is a role for the argon beam device for coagulation of small vessels, analogous to that achieved by cavitating ultrasonic dissection.
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Dissection in the hilum in preparation for resection or during biliary surgery is facilitated by the argon beam coagulator. Troublesome small portal venous tributaries along the bile duct or within hilar areolar tissue are simply and rapidly controlled. Several companies, including Beacon, Valley Labs, and Birtcher, are expanding the utility of these instruments by combining standard electrosurgery units with the argon beam coagula tor. Control at the handpiece achieves a highly versatile instrument capable of coagulating with or without gas flow. Laser-assisted Resection
The CO 2 laser and the neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers have been extensively discussed in the setting of hepatic resection. 5, 17, 18 In the case of the latter, contact tips have extended the usefulness of the cutting characteristics of the laser .15,32,34 Unlike the bare Nd:YAG fiber, the tips provide the feeling of direct tissue contact, which many surgeons find more comfortable. A combination of Nd:YAG and CO 2 lasers in a single unit has been said to achieve a better combination of light frequencies for coagulation and vaporization. 18 The depth of tissue injury by the Nd:YAG laser is approximately 4.0 mm with temperatures as high as 200°C at the site of the contact. 5 With a decrease in hepatic blood flow, which can be achieved with clamping of the hepatic inflow with strapping or with Storm and Lin clamps, the width of the necrotic zone can be increased to 7 or 8 mm. 18 With the clear contact sapphire tip, a very small (2-mm) zone of necrosis occurs. By utilizing frosted tips, a broader zone of necrosis is possible with facilitation of resection through fibrotic liver. 17, 33, 38 This contact laser has a significant advantage over the ultrasonic dissector, which can be nearly useless in a fibrotic liver. The disadvantage of the laser technique is that, as with electrocautery or the cold surgical knife, discrimination of parenchyma from vascular and biliary structures is not possible. With larger vessels in the 2-mm range, cutting without coagulation occurs, thereby increasing blood 10ss.5 Recently, there have been several studies comparing the various techniques of hepatic resection in terms of rapidity of performance of a defined surgical procedure and the success of controlling bleeding. 32, 33, 38 In 1986, Tranberg et al reported, in a comparison of the Nd:YAG laser, the ultrasonic aspirator, and blunt dissection, that there was less tissue damage with the CUSA than with the other two techniques. 38 Extending their work, this group reported in 1987 on utilizing a frosted contact tip with the Nd:YAG laser at 15 W, and continuous duration in a similar comparison. 33 There appeared to be little difference in the blood loss produced with the contact laser and the ultrasonic dissector or the suction knife. Further work by Schroder et al in 1987 indicated that the noncontact laser may cause more extensive tissue damage and is not as good as the contact laser at achieving hemostasis. 32
".
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ij "
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Summary
Surgeons who "grew up" in the era of rapid parenchymal transection using finger fracture or blunt techniques frequently find the newer CUSA and lasers somewhat slow. For these surgeons, it is likely that the argon beam coagulator in conjunction with their usual techniques for parenchymal fracture will meet their needs for speed and hemostasis. For those familiar with CUSA and the laser, the fibrotic liver, once a barrier to effective dissection with the CUSA, can be overcome with blunt dissection techniques or the contact laser. One must bear in mind the theoretical risk of air embolus with the argon beam coagulator or free fiber laser with coaxial gas flow, particularly when working posteriorly near larger hepatic venous tributaries and with relatively high gas flows. Table 1 provides a qualitative comparison of the various techniques used for parenchymal transection. It is important to emphasize once again that the newer technology does not necessarily solve the significant bleeding problems that can develop during hepatic resection. It can be a humbling experience to resect larger tumors that decrease hepatic pliability, or to perform hepatectomy in patients with prior right adrenal or right renal surgery, or to resect tumors that are posteriorly located near the inferior vena cava or hepatic veins. In these instances, the standard vascular surgery techniques of proximal and distal control and careful suturing frequently will be of more value than the technical advances discussed.
INTERSTITIAL THERAPY OR IN SITU ABLATION OF INTRAHEPATIC MALIGNANCIES
For many reasons, patients with intrahepatic malignancies may not be suitable candidates for resection. Systemic metastatic disease and Table 1. QUALITATIVE COMPARISON OF HEPATIC PARENCHYMAL TRANSECTION TECHNIQUES WITHOUT VASCULAR OCCLUSION Visibility of Vascular/Biliary Structures Blunt fracture Blunt fracture & suction Blunt fracture & argon beam coagulator CUSA & suction CUSA & argon beam coagulatQr Contact laser photocoagulation *+ + + +
=
most;
+
=
least.
Rapidity of Performance
Blood Loss*
Cost*
Poor Fair Fair
Rapid Rapid Rapid
++++ ++++ +++
+ + ++
Good Very good
Slow Slow
++ +
+++ ++++
Fair
Intermediate
+++
+++
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intra-abdominal disease outside the liver account for the bulk of the contraindications. While it appears that resection of as many as three or four lesions in the liver may be associated with longevity in the setting of metastatic colorectal cancer,15 the location of one or two lesions within the liver may be such that resection is not possible. In addition, frequently, there are patients with medical illnesses that make them unsuitable for major liver resection. In recent years, it has also become apparent that patients with metastatic neuroendocrine tumors, such as carcinoid and gastrinoma, may achieve substantial symptomatic benefit by the ablation of hepatic metastases even when the primary or every metastatic site is not ablated. Investigators have searched for a means to treat liver lesions in situ in such a fashion that the disease is controlled and the complications minimized. Impetus has been given to the possible role of in situ tumor treatment by accumulated evidence, summarized in the data from the Hepatic Tumor Registry, that the expected benefits of resection apply also to patients who have surgical margins as close as 1 em around the metastatic lesion. 15, 16 The same type of information about margins is not available for primary hepatocellular carcinoma. However, there is extensive evidence for the palliative benefit of localized resection in these hepatoma patients, who are frequently not candidates for major liver resection because of extensive cirrhosis coincident with their cancer. Thus, the goal of effective in situ treatment with margins that might allow a cure has been pursued by several investigators (Fig. 1). Techniques for the interstitial treatment of these hepatic tumors include alcohol injection, cryosurgery, laser ablation, laser hyperthermia, electrodesiccation, and interstitial radiation implantation. In order to understand the place of laser hyperthermia in this treatment armamentarium, these methods will be briefly discussed. First, it is useful to consider a technique for selective photovaporization of liver tumors. Although not a resection technique, it is an in situ attempt to ablate individual liver lesions, and it is based on the premise that a cure is a very real goal of in situ techniques if one can achieve a proper margin.
Selective Photovaporization of Liver Tumors
The liver is mobilized to obtain exposure and allow access to the lesion in question. The liver capsule is scored with the electrocautery or the laser in a circular fashion directly over the lesion (Fig. IA). This is the base of a cone of dissection: the apex of the cone is the metastasis to be treated. A broad base is necessary for deeper and larger lesions. Parenchymal dissection is carried toward the lesion in a cone-like fashion to expose the lesion (Fig. IB). The relation of the lesion to the hepatic veins and portal tracts is carefully considered. Once the lesion has been exposed in this manner, one can vaporize it safely under direct vision (Fig. IC). An Nd:YAG laser with a bare fiber is used for this purpose. The laser power setting is approximately
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A
B Figure 1. Technique of selective photovaporization. A, Deep-seated hepatic metastases are approached by first scoring the liver capsule, thus creating the base of a cone of dissection. B, Dissection of the cone of hepatic parenchyma ends approximately 1 cm from the hepatic metastasis, which is the apex of the cone. Illustration continued on opposite page
80 W applied as a continuous beam, with the laser fiber being held 1 cm from the lesion being treated and applied until vaporization of the lesion occurs. A specialized smoke evacuator is necessary to remove the rather pungent laser plume. A 1- to loS-cm cuff of normal tissue is included in the field of vaporization to ensure adequate margins (Fig. 1D).
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c
D Figure 1 (Continued). C, Photoablation is accomplished with a bare-fiber Nd:YAG laser. 0, The goal of vaporization is to achieve a minimum of a 1-cm margin around each hepatic metastasis.
The appearance of the walls of the cavity is carefully noted, and any bleeding or bile leak is managed by suture ligation or repair. Particular attention must be directed to preservation of bile drainage of the remaining segments of the liver, as disruption of the biliary drainage of a substantial portion of the liver will ensure the development of a troublesome biliary fistula in the postoperative period. A closed, active drain is left for a few days to manage blood, lymph, and bile drainage.
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Hilar control without temporary occlusion or ligation of the hepatic blood supply will usually allow safe resection, especially if the CUSA is used to dissect to the point at which vaporization is initiated. The key to safe laser photoablation is adequate exposure of the entire metastasis during the vaporization. The broad-based cone provides clear visibility of the walls of the tumor site after ablation, so that damaged biliary and vascular structures can be repaired. While offering tumor ablation to a few patients unable to undergo resection, laser photoablation is technically time consuming and difficult. Direct vision to avoid bleeding requires a large dissection even to approach the lesion for vaporization. When considering these factors, the following interstitial therapies appear more promising. General Comments Regarding Interstitial Techniques
The use of interstitial or in situ therapies has been driven by the fact that most patients who undergo liver resection for either metastatic disease or hepatocellular carcinoma will ultimately succumb to their cancer. If a relatively safe means could be employed to ablate lesions and possibly cure the few patients who are curable and, at the same time, reduce the morbidity and mortality rates of the therapy, most such patients would be better served. Improved hepatic imaging, in particular the development of realtime ultrasound, has enabled radiologists to visualize lesions in the range of 2.0 cm rather easily percutaneously. Employing intraoperative ultrasound, resolution can be further improved. Ultrasound is useful both for identifying the site of a metastasis and for placing an interstitial treatment modality into the tumor site. Ultrasound aids in defining the margins of the tumor site and can be used to monitor the ongoing effects of tissue damage such as thermal or freeze injury. The tracking of alcohol into the liver interstitium after ethanol injection can also be monitored with ultrasound. Follow-up analysis by CT, MR imaging, or ultrasound can then be employed as an absolute anatomic indicator of treatment effectiveness. The use of tumor markers such as carcinoembryonic antigen, alpha-fetoprotein, or neuroendocrine secretory products can also be used as an indirect means of assessing the efficacy of treatment, although radiologic imaging is the preferred method for assessing the response to therapy. Description of Treatments Cryotherapy
In 1987, Ravikumar et al reported their experience with hepatic cryosurgery for disease from colon cancer metastatic to the liver. 31 Despite the use of cryosurgery to treat a variety of neoplasms at various body sites, it was only with improvement in technology and the ability
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to use an 8- and 12-mm liquid nitrogen-cooled probe that could be placed interstitially at surgery that the treatment could be delivered effectively to deep sites. Verification of the effectiveness of therapy could be obtained anatomically by using real-time ultrasound to measure the size of the growing ice ball caused by freezing. Freezing and thawing for three cycles was an effective means of ensuring tumor necrosis. 28, 30 The general size of the lesions treated by this group was less than 3.0 cm. Zhou et aI, in the following year, reported an experience using cryosurgery with hepatocellular carcinoma. 39 Sixty patients were treated using surface freezing with hemispherical areas of necrosis of 9 cm diameter with a 6-cm probe or 6-cm areas of necrosis with a 3-cm probe obtained by placing the freezing plate onto the surface of the liver. Survival appeared to be improved in 27 cases treated with cryosurgery alone, with a 2-year survival rate of 23% and a 5-year survival rate of 4%, although this represents a select group of patients. Three papers report a total of 35 patients forming the bulk of current registered cryotherapy experience with metastatic disease. 28, 30, 31 Smaller lesions «4.0 cm) appear to respond well, and survival data from uncontrolled series appear promising. The disadvantage of cryotherapy appears to be that it requires an operation in order to place the large probes near the lesions. Thus, the morbidity of a surgical procedure must be factored into the analysis of morbidity and mortality rates. The treatment has generally been safe, with no frequent treatment-associated complications having been recorded. Air embolus can occur with the technique of interstitial treatment via the tract of the dilator required to place the cryoprobes, and an unusual nitrogen embolus has been described. 25, 28 Bleeding after freeze-thaw "cracking" of the liver and myoglobulinuria have been reported in isolated instances. 25, 28, 30 Vessels tolerate cooling well, but bile duct stricture or occlusion occurs readily. Alcohol Injection
There is a rising tide in enthusiasm for percutaneous introduction of absolute ethanol into lesions by a fine needle utilizing ultrasonic guidance. With ethanol injection, extensively reported on by Livraghi and Shiina and their coworkers, complications were rare except for occasional pain associated with extravasation of alcohol into the peritoneal cavity. 20-22, 36 Systemic alcohol injection is unlikely to occur. The difficulty with embracing the concept of alcohol therapy enthusiastically is the well-established fact that when alcohol is administered, its distribution is not geometrically predictable. 25 The material tracks along tissue planes of least resistance and, in particular, misses areas of tumor characteristically fibrotic or encased in the fibrotic liver. Metastatic lesions in particular are prone to incomplete destruction. 21 In addition, whereas the distribution of the alcohol can be tracked ultrasonically, the biologic effect-that is, tumor necrosis-cannot be monitored by ultrasonic guidance until actual tumor necrosis has occurred, as confirmed by follow-up studies 2 or more weeks after
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treatment. Additionally, the problem of being unaware of the extent of biologic effectiveness creates problems in planning treatment and identifying areas for injection and the volume of alcohol to be injected so that larger lesions can be treated. 25 However, the general consensus is that survival rates are quite acceptable in that the treatments may be performed two, three, or more times to create effective necrosis of a given tumor. In fact, repeated treatments are probably mandatory in view of the difficulty in predicting how much alcohol is required to infarct a given tumor mass. It is generally agreed that lesions smaller than 3 cm are the most amenable to this treatment, although it should be emphasized that relatively few patients have been studied. The four largest experiences 2o, 21, 35, 36 total 225 cases (211 cases of hepatoma, 14 cases of metastatic disease), although there are many smaller series reported in abstract form discussing this evolving technology. The chief advantages are low cost, ease of administration, and low toxicity. Combination with transcatheter embolization may extend the utility of the technique. Interstitial Radiotherapy
Little information exists about interstitial or brachytherapy of intrahepatic malignancies despite the known utility of the technique for tumors close to the body surfaces and employment at laparotomy for advanced disease. The two methods-implantation of the tumor with radioactive sources or employment of afterloading catheters that can be used to guide radiation source placement-have benefited from technical advances in computer planning, stereotactic guidance of catheter placement, and high-speed computerized source placement via afterloading catheters. However, treatment of liver tumors reported thus far has relied on ultrasound-guided placement of catheters or radioactive sources in only a few patients. 6 The effects of therapy can only be monitored over time with follow-up imaging. Interstitial Laser Hyperthermia
Clinically, Hashimoto et aI, in 1985,13 were the first to apply the concept of interstitial thermal injury utilizing laser light. They recognized that light administered by the Nd:YAG laser could deliver energy at the tip of a transmission fiber placed interstitially. Previous experimental work by others had established that the injury is a spherical lesion at the tip of the fiber, which, as with the modalities discussed above, can be followed using real-time ultrasound. Since this report, others, including Hahl et aI, established that the technique can be safe; and, as with percutaneous ethanol injection, the laser fibers can be inserted via percutaneously placed 14-gauge needles introduced under ultrasonic guidance. l l The extent of the thermal injury is determined, as in all laser techniques, by the power in watts and the exposure time as well as by
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the characteristics of the light wavelength and intensity and the absorption characteristics of the tissue. In general, using. the Nd:YAG laser, the power applied has ranged from 0.5 W to 6.0 W. Exposure times have ranged from 500 to 1000 seconds. An advantage within the liver (especially with tumors located near major vascular structures one wishes to preserve) is the thermal protection afforded by blood flow, which will save major vessels from injury. Therefore, the technique has potential application for lesions near structures that will make them surgically unresectable. 25 However, heat does have the potential for causing bile duct injury leading to obstruction or narrowing. An additional danger is related to the power setting, as has been reported by Schroder and associates. With the Nd:YAG laser at low power settings, in the range of 0.5 to 1.5 W, no cooling is needed. However, if 4 to 6 W of power is applied to decrease the exposure time, most investigators have used coaxial gas flow in the range of 1 LI minute to provide cooling. The application of heat and gas under pressure in a closed space has led to a fatal air embolism. 33 It does appear that the lower power settings will at least have the advantage of diminishing the risk of embolus, as gas cooling is not required. The tiijle required for creating therapeutic heat injury will be longer, however. To ensure total ablation of larger lesions, one must carefully place a pattern of fibers such that the entire tumor is encompassed. A spread or pattern of laser fibers can achieve this effect. The principal advantage of this technique is that the extent of the necrosis can be monitored with real-time ultrasound and adjusted at the time of treatment. Also, the injury is predictably spherical, unlike the irregular lesions resulting from alcohol injection. 2 Radiofrequency Electrodesiccation
In 1990, McGahan et al published their experience utilizing a standard electro surgical generator to apply radiofrequency energy in an interstitial fashion via a percutaneously introduced fine needle sheathed in nonconductive plastic. 26 The bare 1.0-cm tip was placed with ultrasonic guidance in the desired area of treatment. During the power application and monitoring of the effect with real-time ultrasound, spherical defects are created with diameters directly correlated with the power applied from the electrosurgical generator. This remains an experimental technique but is being performed in the clinical research setting and may prove ultimately to be an inexpensive and efficacious way to treat hepatic tumors. Complications
The introduction of probes into the interstitium and large areas of resulting necrosis may predispose to infection. With a variety of
~ a.
Table 2. COMPARISON OF TECHNIQUES FOR IN SITU HEPATIC TUMOR ABLATION*
Criterion Ease of application Precision and predictability Ease of real·time monitoring Accessibility of ail liver Treatment frequency Ease of retreatment Equipment expense Hospitalization time Staff required
• + ++ + +
Percutaneous Alcohol Injection
Percutaneous Laser Hyperthermia
++ + + ++ +
+ ++++ ++++ +++++ ++++ + +++ +
+++++ +++ ++ ++++ ++ ++++ +++++ +++++
++++ ++++ ++++ ++++ +++ ++++ + ++++
Surgeon anesthesiologist, OR staff
Surgeon anesthesiologist, OR staff
interventional radiologist
interventionai radiologist
Laser Vaporization
+ ++++ Direct vision
= greatest advantage.
Cryotherapy
Percutaneous Interstitial Radiotherapy
++ +++
Percutaneous Radiofrequency Electrodesiccation
+++ ++++ +++
++++ ++++ ++++ ++++ +++ ++++ +++ ++++
Interventional radiologist, physicist, radiation therapist
Interventional radiologist, possibly anesthesiologist
Not possible
++++ Unknown
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transcatheter embolization techniques, larger tumors that become necrotic have increased rates of infection. Thus, antibiotic prophylaxis and monitoring for infection are required in any of these patients receiving interstitial therapies. Although complications appear to be surprisingly few in the short term and the discomforts of the procedures are well tolerated by most patients, the potential for biliary toxicity from heat or alcohol with stricturing and bile duct occlusion must be considered. In addition, with thermal techniques, although it is established that healing of the areas occurs by contraction and fibrosis, one must be alert to the possibility and long-term risk of hemobilia. Summary
Table 2 provides a comparison of these interstitial and in situ techniques, assessing several criteria and utilizing and expanding on an excellent review by Masters et al. 25 The rapid advance of technology and cross-fertilization between groups using different interstitial techniques will lead to a clear understanding of the benefits and limits of each. However, there is essentially no information at the present time to suggest that these techniques should be used in lieu of hepatic resection in an attempt to cure patients who are good operative risks. There are insufficient data of a controlled nature to determine that there has been a survival or palliative benefit in many of the patients so treated. Nevertheless, as it is clear that these treatments cause tissue destruction in an appropriate nonmorbid way and that they are well tolerated with low risk to the patients, it is entirely conceivable that interstitial techniques will replace hepatic resection in some instances in the future, particularly for lesions smaller than 3 cm. References 1. Baer HU, Maddem GI, Blumgart LH: New water-jet dissector: Initial experience in hepatic surgery. Br J Surg 78:502-503, 1991
2. Bosman S, Phoa SSK, Mosma A, et al: Effect of percutaneous interstitial thermal laser on normal liver of pigs: Sonographic and histopathologic correlations. Br J Surg 78:572-575, 1991
3. Brown DA, Pommier M, Woltering EA, et al: Nonanatomic hepatic resection for secondary hepatic tumors with special reference to hemostatic technique. Arch Surg 123:2063-2066, 1980
4. Campra JL, Reynolds TB: The hepatic circulation. In Arias I, Popper H, Schacter 0, et al (eds): The Liver: Biology and Pathobiology. New York, Raven Press, 1982, pp 627-645
5. Dixon JA: General surgical applications of lasers. In Surgical Application of Lasers. Chicago, Year Book Medical Publishers, 1987, pp 119-143 6. Dritschilo A, Grant EG, Harter KW, et al: Interstitial radiation therapy for hepatic metastases: Sonographic guidance for applicator placement. AJR 146:275-278, 1986 7. Ebara M, Ohto M, Sugiura N, et al: Percutaneous ethanol injection for the treatment of small hepatocellular carcinomas: Study of 95 patients. Gastroenterology 5:616-626, 1990 8. Foster J: Liver resection techniques. Surg Clin North Am 69:1-250, 1989
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9. Goldberg SM, Gordon PH, Nivatvongs S: The basic application of electrosurgery. In Essentials of Anorectal Surgery. Philadelphia, JB Lippincott, 1980, pp 229-233 10. Haapiainen R, Schroder T: The suction knife in liver surgery. Am J Surg 157:340342, 1989 11. Hahl J, Haapiainen R, Ovaska J, et al: Laser-induced hyperthermia in the treatment of liver tumors. Lasers Surg Med 10:319-321, 1990 12. Hardy KJ, Martin J, Fletcher DR, et al: Hepatic resection: Value of operative ultrasound and ultrasonic dissection. Aust NZ J Surg 59:621-623, 1989 13. Hashimoto D, Takami M, Idezuki M: In depth radiation therapy by Nd:YAG laser for malignant tumors of the liver under ultrasonic imaging [abstract]. Gastroenterology 88:AI663, 1985 14. Hernandez AD, Smith JA, Jeppson KGB, et al: A controlled study of the argon beam coagulator for partial nephrectomy. J Urol 143:1062-1065, 1990 15. Hughes KS, Rosenstein RB, Songhorabodi S, et al: Resection of the liver for colorectal carcinoma metastases: A multi-institutional study of long-term survivors. Dis Colon Rectum 31:1-4, 1988 16. Hughes KS, Simon R, Songhorabodi S, et al: Resection of the liver for colorectal carcinoma metastases: A multi-institutional study of patterns of recurrence. Surgery 100:278-284, 1986 17. Joffe SN: Contact YAG laser system in abdominal surgery, in particular hepatic and pancreatic surgery. Semin Surg Oncol 5:48-56, 1989 18. Joffe SN: Liver resection. In Lasers in General Surgery. Baltimore, Williams & Wilkins, 1989, pp 100-124 19. Lanzifame RJ, Qiu K, Rogers DW, et al: Comparison of local tumor recurrence following excision with the CO, laser and argon beam coagulating laser. Lasers Surg Med 8:515-520, 1988 20. Livraghi T, Vettori C: Percutaneous ethanol injection therapy of hepatoma. Cardiovasc Intervent Radiol 13:146-152, 1990 21. Livraghi TG, Vettori C, Lazzaroni S: Liver metastases: Results of percutaneous ethanol injection in 14 patients. Radiology 179:709-712, 1991 22. Livraghi T, Festi D, Monti F, et al: US-guided percutaneous alcohol injection of small hepatic and abdominal tumors. Radiology 161:309-312, 1986 23. Longmire WD, Tompkins RK: Manual of Liver Surgery. New York, Springer-Verlag, 1981 24. Mason GR: Hepatic resection technique. Am J Surg 157:343-345, 1989 25. Masters A, Steger AC, Brown SG: Role of interstitial therapy in the treatment of liver cancer. Br J Surg 78:5189-523, 1991 26. McGahan JP, Browning JP, Brock JM, et al: Hepatic ablation using radiofrequency electrocautery. Invest Radiol 25:267-270, 1990 27. Mies S, Raia S: A simple method for controlling hemorrhage during hepatectomy. Surg Gynecol Obstet 168:265-266, 1989 28. Onik G, Rubinsky B, et al: Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon carcinoma: Preliminary results. Cancer 67:901-907, 1991 29. Rappaport AM: Physioanatomic considerations. In Schiff L, Schiff ER (eds): Diseases of the Liver. Philadelphia, JB Lippincott, 1982, pp 1-57 30. Ravikumar TS, Steele GD: Hepatic cryosurgery. Surg Clin North Am 69:433-440, 1989 31. Ravikumar TS, Kane R, Cady B, et al: Hepatic cryosurgery with intraoperative ultrasound monitoring for metastatic colon carcinoma. Arch Surg 122:403-409, 1987 32. Schroder T, Brackett K, Joffe SN: An experimental study of the effects of electrocautery and various lasers on gastrointestinal tissue. Surgery 101:691-697, 1987 33. Schroder T, Hasselgren P-O, Brackett K, et al: Techniques of liver resection: Comparison of suction knife, ultrasonic dissector, and contact Nd:YAG laser. Arch Surg 122:1166-1171, 1987 34. Schroder TM, Puolakkainen PA, Hahl J, et al: Fatal air embolism as a complication of laser-induced hyperthermia. Lasers Surg Med 9:183-185, 1989 35. Sheu Jc, Sung JL, Huang GT, et al: Intratumor injection of absolute ethanol under ultrasound guidance for the treatment of hepatocellular carcinoma. Hepatogastroenterology 34:255-261, 1987
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36. Shiina 5, Tagawa K, Unuma T, et al: Percutaneous ethanol injection therapy of hepatocellular carcinoma: Analysis of 77 patients. AJR 155:1221-1226, 1990 37. Tanaka K, Okazaki H, Nakamura S, et a1: Hepatocellular carcinoma: Treatment with a combination therapy of transcatheter arterial embolization and percutaneous ethanol injection. Radiology 179:713-717, 1991 38. Tranberg KG, Rigotti P, Brackett KA, et al: Liver resection: A comparison using the Nd:YAG laser, an ultrasonic surgical aspirator, or blunt dissection. Am J Surg 151:368373,1986 39. Zhou X-D, Tang ZY, Yu YQ, et al: Clinical evaluation of cryosurgery in the treatment of primary liver cancer. Cancer 61:1889-1892, 1988
Address reprint requests to Philip D. Schneider, MD, PhD The University of California Davis Cancer Center Division of Surgical Oncology Department of Surgery 4501 X Street Sacramento, CA 95817