Hepatobiliary Surgery - part 9 ppt

Patients at high-risk may include those presenting withsynchronous colon and hepatic disease, hepatic metastases within 24 months of theprimary tumor, or patients undergoing hepatic rese

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When Should HAIP Therapy Be Considered?

At present, HAIP therapy is limited to clinical trials Various drug regimens andcombinations are under investigation; for the purpose of the present discussion,only issues pertaining directly to hepatic artery pump placement are reviewed.Clinical scenarios in which an HAIP is considered include:

1 Liver resection and colectomy in combination with HAIP placement

2 Liver resection in combination with HAIP placement

3 HAIP placement alone, without liver resection or colectomy

4 Nonsurgical ablative therapy in combination with HAIP placement.The rationale for the use of HAIP chemotherapy is to provide regional treat-ment for patients considered to be at high-risk for the local recurrence, progression,

or persistence of disease Patients at high-risk may include those presenting withsynchronous colon and hepatic disease, hepatic metastases within 24 months of theprimary tumor, or patients undergoing hepatic resection with minimal free margins

or demonstrated persistent disease

Nonresectional hepatic ablative therapies (e.g., radiofrequency ablation,cryoablation), for patients not otherwise candidates for surgical resection, have beenpopularized by the early promising results demonstrated in small series In thesepatients, HAIP therapy may be used as a component of their treatment However,the long-term outcome for this approach remains to be established

Preoperative Patient Evaluation

This section will be necessarily brief, as the topic of metastatic work-up for patientswith colorectal cancer is covered elsewhere Patient eligibility for enrollment intoclinical trial is specifically defined by the study protocol In general, the followingcriteria are common to most HAIP clinical trials:

• History of histologically confirmed colorectal adenocarcinoma metastatic

to the liver with no clinical or radiographic evidence of extrahepatic disease

• Liver metastases must comprise < 70% of the liver parenchyma

• WBC >3,500 cells/mm3 and platelet count > 150,000 cells/mm

• Albumin >2.0 gm%

• Total serum bilirubin < 2.0 mg/dl

• No active concurrent malignancies

• No active infection, ascites, or hepatic encephalopathy

• Prothrombin time within 1.5 seconds of normal

Furthermore, patients meeting these criteria must have favorable vascular anatomyfor HAIP placement

HAIP placement requires that a catheter (Fig 17.1) be introduced into the troduodenal artery (see following section, technique for placement of HAIP), sothat pump flow is directed necessarily towards the liver via the hepatic artery(s).Traditionally, demonstration of the arterial anatomy has been done by celiac (visceral)angiography This approach is invasive, has some (albeit low) associated morbidity,and is time consuming for the patient More recently, magnetic resonance angiogra-phy (MRA), which is noninvasive and devoid of the angiography-associated mor-bidities, is being developed At the present time, the radiographic images obtainable

gas-229Technique for Placement of the Hepatic Arterial Infusion Pump

stan-Surgical Technique for the HAIP Placement

Patients should receive prophylactic preoperative gram-positive antibiotic age and this should be continued for 24 hours following the operation Operativedraping of the patient for this procedure should extend cranially to the nipple lineand inferiorly to the symphysis The skin is prepared with a bactericidal such as aBetadine or Hibiclens solution The skin is dried with an absorbent sterile towel and

cover-a providone-iodine cover-adhesive drcover-ape is plcover-aced on the opercover-ative field We prefer the use

of a right subcostal incision extended slightly beyond the midline This approachprovides ample exposure to the right upper quadrant and spares the left side of theabdomen for the creation of the pump pocket (Fig 17.3)

Intra-abdominal adhesions will be present in patients who have previouslyundergone colectomy Some of these adhesions will need to be cleared to preventinadvertent injury during retraction, dissection, or when passing the pump catheteracross the abdomen from within the peritoneum

Cholecystectomy is routinely performed to prevent chemical cholecystitis Thehepatic artery is easily identified in the porta hepatis, both by location and palpabletell-tale arterial thrill Favorable anatomy for pump placement has been verifiedprior to coming to the operating room by angiogram or MRA

Fig 17.1 Visceral angiogram: (gastroduodenal artery, left hepatic artery, righthepatic artery)

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Fig 17.2 Visceral MRA: (gastroduodenal artery, left hepatic artery, right hepatic artery

Fig 17.3 Planned incision for laparotomy (right sub-costal) and pump placement(left sub-costal)

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The gastroduodenal artery (GDA) is located immediately inferior to the properhepatic artery coursing inferiorly towards the proximal duodenum (Figs 17.1 and17.2) Sharp dissection to isolate the GDA is performed, taking care to ligate or clipthe surrounding lymphatic vessels The common bile duct (CBD) lies lateral to theGDA, and injury to the CBD must be avoided during the dissection Medially anddeep to the GDA lies the portal vein, and again, great care is needed while dissecting

in this area

After circumferentially dissecting the GDA, a right angle instrument is used tofacilitate the passing of a suture ligature around this vessel This suture will be usedfor traction as arterial branches are cleared off for approximately 1 cm towards theduodenum and head of the pancreas, 1 cm toward the proximal common hepaticartery, and 1 cm towards the bifurcation of the hepatic artery (but proximal to theright and left divisions)

Up to 15% of patients may have an accessory left hepatic artery arising from theleft gastric artery, which should be (but is not always) identified by the preoperativeimaging In order to maintain drug-only arterial blood flow to the liver, this vesselmust be identified and ligated Elevation of the left lobe of the liver to assess for thepresence of a nonvisualized left hepatic artery is mandatory This is best accomplished

by dividing the lesser omentum with ligation of the accessory vessel if it is present.Once this is accomplished, arterial flow from the GDA should be only towardsthe liver via the common hepatic artery and the liver should receive only drugscontaining blood flow

Considerations for Patients with Variant Anatomy

The technique previously described is applicable only for patients with standardarterial anatomy As discussed, it is important to identify any aberrant arterial archi-tecture By definition, accessory vessels are present, in addition to the normal ana-tomic structures, such that ligation and division of an accessory right or left hepaticartery can be performed without ischemic consequences In contrast, replaced arter-ies may represent the sole arterial supply to a given lobe of the liver

Prior to ligation and division, replaced arteries should be clamped with anoncrushing vascular clamp to assess for potential liver ischemia If no obviousischemia is noted, the vessel can be ligated However, at least one artery to eitherlobe of the liver arising from the hepatic artery after the take-off of the GDA must

be preserved Crosshepatic arterial perfusion to the contralateral lobe of the liverdevelops rapidly after ligation of the replaced lobar artery in the patient with anontoxic liver In contrast, if ischemic changes are observed during “trial-clamping”,then that vessel should be preserved and cannulated separately to maintain adequatehepatic perfusion

Replaced Right Hepatic Artery (RRHA)

The most common variant arterial anatomy is a replaced RHA with a standardleft hepatic artery (LHA) and GDA A RRHA is most commonly identified bypalpation as it exits from behind the duodenum, courses lateral to the common bileduct, and posteriorly within the hepatoduodenal ligament The RRHA has no sidebranches that can be used to insert the catheter; however, arteriotomy or directpuncture under vascular control can be used for placement of a polyethylene or 22

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gauge “angiocatheter” with subsequent connection to the HAIP catheter Placingthe catheter directly in the RRHA, and ligating the LHA, results in the develop-ment of crossover perfusion of the left lobe of the liver Another approach is theplacement of a double-catheter pump where one catheter is placed into the LHAfrom the GDA and the second catheter is inserted directly into the RRHA to assurebilateral perfusion The latter is the approach we prefer when possible

Replaced Left Hepatic Artery (RLHA)

A RLHA can be identified coursing within the gastrohepatic ligament along theinferior edge of the liver The RLHA arises from the left gastric artery (LGA) and there

is a normal RHA In this setting, the HAIP catheter can be inserted into the GDA toperfuse the RHA with ligation of the RLHA Another technique is the placement of adouble-catheter pump, where one catheter is inserted into the LGA to perfuse theRLHA and the other catheter is inserted into the GDA to perfuse the RHA

Trifurcation of the Common Hepatic Artery (CHA)

into RHA, LHA and GDA

Trifurcation of the CHA into a RHA, LHA and GDA is another described tomic variant that can be managed by inserting the HAIP catheter into the GDA

ana-1 cm proximal to the takeoff of the GDA from the CHA to allow for adequate blood mixing The GDA is then ligated Although feasible, this approach is associ-ated with an increased risk for CHA thrombosis Alternatively, insertion of the HAIPcatheter into the splenic artery, advancing it into the CHA with ligation of the GDAand left and right gastric arteries, will obtain bilateral perfusion A more complexapproach to deal with this anatomy is to construct a conduit using a short segmentvein graft for catheter insertion into a selected artery with subsequent ligation of theother vessels We do not recommend this latter approach

drug-These variant arterial anatomies underscore the importance of preoperativeassessment of vascular anatomy in order to be prepared at the time of operation.Failure to appropriately identify and ligate aberrant arteries and arterial branchesmay result in malperfusion

Creation of the Subcutaneous Pump Pocket

The pump pocket is usually created on the left side of the abdominal wall unless

a colostomy is present The pump is placed well below the left costal margin toprevent patient discomfort from the hard metal pump abutting against the ribs Theskin incision is transverse and should measure no more than 1 cm wider than thewidth of the actual pump to be placed (Fig 17.4) The subcutaneous tissues aredivided using electrocautery up to, but not into, the abdominal wall fascia Continuinginferiorly along the adipose-fascial interface, the pocket is extended for about 8-10

cm (actual pocket size should be planned based on the size of the actual model ofpump to be implanted) Strict attention to hemostasis must be maintained duringthe dissection of the subcutaneous pocket to minimize the risk of hematoma andlessen the risk of subsequent complications

The automatic mechanism that drives catheter flow is initiated (“primed”)

by filling the pump reservoir with a standard volume of heparinized saline(volume is specific to the pump model), which is placed in a warm water bath

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at body temperature to activate it Flow through the catheter is driven by static pressure secondary to internal expansion from thermal activation The deliv-ery mechanism is graduated to deliver a set rate of flow, and adjustment of thesolution concentration regulates the amount of drug delivery

hydro-The pocket is tested for fit of the pump body and catheter while maintaining a

“no-contact” technique with the skin Pump architecture and specifications will varyaccording to manufacturer and model; however, all designs will have a catheter with

an internal component that exits through the pump body (Fig 17.5) This cathetermust be inserted into the abdominal cavity through the anterior abdominal walland subsequently placed into the GDA In performing this maneuver, care should

be taken to avoid injury to vessels coursing through the posterior surface of therectus abdominus muscle

Pumps have anchoring “loops” (Fig 17.5) fused to the pump body housing toprevent “flipping” or axial rotation of the pump, within the subcutaneous pocket.Using a skin retractor, the inferior edge of the pump pocket is elevated towards theceiling; interrupted nonabsorbable sutures are placed into the fascia of the anteriorabdominal wall and passed through each anchor loop The two distal anchors aresutured first and not tied until the two proximal sutures are placed Until the suturesare tied, the ends of the cut suture are held in place by individual clamps Theinferior pump pocket edge is elevated and the distal anchor sutures are tied, pullingthe pump down into the pocket as it is fastened down Care should be taken toinsure that the pump catheter does not become twisted or damaged during thismaneuver With the pump in place, the catheter is free within the abdomen

Fig 17.4 Abdominal CT with HAIP in the left lower quadrant Note that the pumpbody housing rests directly on the fascia

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Fig 17.5 Hepatic artery infusion pump; the catheter exits the pump body housing

at the 6 o’clock position Note the four anchor loops located around the bodyhousing

The catheter is measured and cut sharply such that the tip has an oblique angleand only one of the flanged catheter hubs remains The catheter length should belong enough to reach the junction of the GDA with the hepatic artery but notextend beyond it In this manner, flow-out of the catheter will necessarily go onlytowards the liver

The GDA is ligated in continuity as it enters the duodenum The position ofthis suture will determine the length of artery available for catheter insertion Oncethe catheter is prepared as described above, and the branches off of the GDA andother arteries have been cleared, proximal and distal control of the hepatic artery isobtained using pediatric vascular clamps A #11 scalpel blade is used to incise theanterior wall of the GDA in a transverse fashion An arteriotomy introducer is in-serted into the GDA lumen to facilitate passing of the catheter tip into the vessellumen The catheter is advanced using nontoothed forceps and the previously placedcircumferential traction suture ligature is tied down onto the catheter behind theflanged hub Care is needed to insure that the knot is not too tight as to impede orocclude flow through the catheter We advocate the use of an additional separatesuture to prevent inadvertent arterial dislodgement We place a 4-0 prolene suturethrough the adventitia of the GDA behind the flanged hub of the catheter andcircumferentially encompassing the vessel, again not encroaching on the catheterlumen The distal (outflow) vascular clamp is removed, followed by the proximal(inflow) clamp

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Assessment of Hepatic Perfusion

Intraoperative fluorescein test is generally performed after pump placement toassure liver-only perfusion Using the side port of the pump, approximately 3-5 cc

of fluorescein (nondiluted) are injected, followed by illumination with a Wood’slamp If all the arterial branches have been properly ligated or clipped, only the livershould demonstrate fluorescence Do not aspirate into the pump when injecting it

as this will result in small clot formation and subsequent pump malfunction quently, the pump is flushed with 10 cc of heparinized saline The pump pocket isclosed in two layers using absorbable suture material The abdominal incision isclosed in standard fashion

Subse-Postoperative hepatic perfusion and extravasation (i.e., stomach, duodenum, andspleen) via HAIP is assessed three days postoperatively by a Technetium-labeledmacroaggregated albumin hepatic scan This will confirm liver-only pump perfu-sion and is necessary prior to the initiation of HAIP therapy (Fig 17.6)

Brief Comments on Technical Complications

Analysis of the technical complications associated with hepatic artery infusionpump placement, reveals that HAIP complications can be divided into those occur-ring either early (< 30 days postpump placement), or late (>30 days) (Table 17.1).Furthermore, complications are divided into arterial, catheter, perfusion or pumprelated

Arterial complications include intimal dissection and thrombosis Arterial bosis that occurs early can be salvaged by reoperation and revision of the catheter;thrombosis in the early postoperative period is often salvaged by thrombolytic therapy.Late arterial thrombosis occurs more frequently and is less likely salvaged

throm-Catheter complications included dislodgement or migration of the GDA eter from its original site or out of the artery with or without hemorrhage Catheterdislodgement is a rare occurrence in the early postoperative period; most dislodgementoccurs late Catheter dislodgement may be accompanied by hemorrhage that can belife-threatening Catheter occlusion is a late occurrence and can be salvaged by lytictherapy

cath-Malperfusion is defined as the identification of organ perfusion other than theliver (i.e., stomach, duodenum or spleen) Extrahepatic perfusion can occur withcatheter misplacement or failure to identify and ligate the appropriate arterial branchesoff the GDA If malperfusion is apparent, a patent branch of the common hepaticarterial system that continues to perfuse the distal stomach or duodenum is oftenidentified Once localized, this complication is corrected by laparotomy with liga-tion of the patent branches of the GDA or CHA More recently, patent vessel brancheshave been embolized at arteriography, obviating the need for re-laparotomy

Pump infections are more frequent in the late period (> 30 days postoperatively)and are the pump related complication that most often results in the prematuretermination of therapy However, pump salvage rates of approximately 25% areobtainable for both early and late pump infections

Complications related to local and regional toxicity of the therapeutic agents arewell characterized elsewhere.1,5

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Fig 17.6 Macro-aggregated albumin scan demonstrating pump to liver-only fusion In the top row images the liver is demonstrated immediately The catheter isevident and although the actual pump is not well-visualized, it is located wherethe catheter originates

per-Table 17.1 Early and late technical complications of HAIP ( n=391) 6

Arterial thrombosis 10 (1%) 6 (2%) 15 (4%) 14 (4%)Catheter dislodgement 3 (1%) 2 (1%) 22 (6%) 12 (3%)

16 months (range 1-110) A total 3% early and 9% late technical failure rates wereobserved The prevention of late arterial thromboses and catheter dislodgementwould prevent the majority of premature treatment terminations related to pumpcomplications

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Summary

In the absence of efficacious systemic chemotherapy regimens to treat hepaticcolorectal metastases, regional therapies will continue to be investigated HAIP place-ment has a low associated mortality; however, the challenge for the surgeon in themanagement of these patients is to provide a reliable system for the administration

of regional chemotherapy The efficacy of hepatic artery infusion pump (HAIP)chemotherapy for metastatic colorectal cancer confined to the liver is currently thesubject of several national multi-center randomized trials

Selected Reading

1 Allen Mersh, TG, Earlam S, Fordy C, Abrams K, Houghton J Quality of life andsurvival with continuous hepatic-artery floxuridine infusion for colorectal livermetastases [see comments] Lancet 1994; 344:1255-6000

2 Chang AE, Schneider PD, Sugarbaker PH et al A prospective randomized trial ofregional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in thetreatment of colorectal liver metastases Ann Surg 1987; 206:685-933

3 Ensminger WD, Rosowsky A, Raso V et al A clinical-pharmacological evaluation

of hepatic arterial infusions of 5-fluoro-2'-deoxyuridine and 5-fluorouracil cer Res 1978; 38:3784-3922

Can-4 Grage TB, Vassilopoulos PP, Shingleton WW et al Results of a prospective domized study of hepatic artery infusion with 5-fluorouracil versus intravenous5-fluorouracil in patients with hepatic metastases from colorectal cancer: A Cen-tral Oncology Group study Surgery 1979; 86:550-555

ran-5 Kemeny N, Daly J, Reichman B et al Intrahepatic or systemic infusion offluorodeoxyuridine in patients with liver metastases from colorectal carcinoma Arandomized trial Ann Intern Med 1987; 107:459-655

6 Dudrick PS, Picon A, Paty PB et al Technical Complications Associated withHepatic Arterial Infusion Pumps for Metastatic Colorectal Cancer (In Prepara-tion)

7 Sigurdson ER, Ridge JA, Kemeny N et al Tumor and liver drug uptake followinghepatic artery and portal vein infusion J Clin Oncol 1987; 5:1836-400

8 Wagner J S, Adson MA, Van Heerden JA et al The natural history of hepaticmetastases from colorectal cancer A comparison with resective treatment AnnSurg 1984; 199:502-588

9 Weiss GR, Garnick MB, Osteen R et al Long-term hepatic arterial infusion of5-fluorodeoxyuridine for liver metastases using an implantable infusion pump JClin Oncol 1983; 1:337-444

10 Wingo PA, Ries LA, Rosenberg HM et al Cancer incidence and mortality, 1995: a report card for the U.S Cancer 1998; 82:1197-2077

Cryotherapy and Radiofrequency Ablation

Ronald S Chamberlain and Ronald Kaleya

Introduction

The liver is a frequent site of both primary and metastatic tumors Surgical tion, and in rare instances liver transplantation, remain the only treatments associ-ated with prolonged survival and in some cases cure Unfortunately, less than 25%

resec-of patients with either hepatocellular cancer (HCC) or metastatic colorectal cancerpresent with liver-only disease and are candidates for surgical resection The inabil-ity of surgery to impact on the survival of most patients with malignant tumors ofthe liver has been the impetus behind the development of multiple alternative treat-ment modalities Tumor histology, stage and site of the primary tumor, extent ofhepatic parenchymal involvement, presence of extrahepatic disease, and the clinicalcondition of the patient influence the appropriateness of the various alternative treat-ments Available alternatives include hepatic artery chemotherapy (Chapter 17) he-patic arterial embolization or chemoembolization (Chapter 4), percutaneous ethanolablation (Chapter 4), cryotherapy (percutaneous, laparoscopic, or open techniques),and thermal ablation that includes radiofrequency, microwave, and laser ablation.Nearly all of these modalities can be performed percutaneously or by using mini-mally invasive techniques This Chapter will focus on the indications, techniques,and complications associated with cryotherapy and radiofrequency thermal abla-tion Suffice it to say the clinical efficacy of both techniques remains unproven, andthe subject of considerable on-going study Based upon this data, several prospectiveand retrospective analyses have demonstrated that liver failure is the primary cause

of death in up to 90% of these patients Non-resectional hepatic ablative strategieshave been developed in an attempt to alter either the course of the disease and/orcause of death in patients with unresectable liver tumors

Indications for Non-Resectional Ablative Therapies

Histology

Hepatocellular Carcinoma

Primary liver cancer is the most common malignancy in Southeast Asia andAfrica and remains the leading causes of cancer-related deaths world wide Each yearthere are approximately 1.2 million cases of HCC in the world with 1 million deaths.While relatively rare in the United States (16,000 cases per year), the mortality is

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nevertheless greater than 90% Among patients with HCC, only 15 to 25% areoperable at presentation and even fewer patients are resectable with curative intent.Despite this fact, the majority of patients with unresectable disease have tumor con-fined to the liver In a report by Farmer et al from the Dumont-UCLA Liver Trans-plant Center, 70% of patients with HCC had disease localized to the liver and only24% were candidates for hepatic resection; these figures clearly demonstrate thecentral role that ablation therapy can play in the treatment of hepatic tumors

Metastatic Disease

The liver is one of the most common sites of metastatic spread for many cancers,particularly gastrointestinal malignancies Unfortunately, most malignancies thatspread to the liver also spread elsewhere making regional ablative therapies unsuit-able Colorectal cancer represents a unique exception to this rule, in that up to one-third of patients with metastatic colorectal cancer may have liver only metastases.Despite occasional reports of high rates of resectability (> 50%), in reality only asmall proportion of patients with metastases confined to the liver are operable due

to limitations imposed by tumor characteristics and patient co-morbidities Severalauthors have estimated that only 8 to 12% of all patients who develop liver me-tastases from colorectal primaries are resectable for cure While the percentage ofpatients who may be candidates for non-resectional ablative therapies is unknown,

it is probably in the area of 15-20%

Non-resectional therapeutic approaches have been applied anecdotally to a ety of other tumor histologies in addition to colorectal cancer These include, butare not limited to, metastases from gastric, pancreatic, esophageal, thyroid, neu-roendocrine, melanoma, renal cell, and sarcoma The application of ablative thera-pies to treat these tumors should be considered extremely experimental and cannot

vari-be advocated outside of a clinical trial The only exception to this rule may vari-be theuse of radiofrequency ablation for the treatment of metastatic neuroendocrine tu-mors for which a considerable body of literature is emerging

Additional Indications and Contraindications

Absolute indications and contraindications for cryotherapy and RFA remainundefined As a general rule, most experienced centers advocate treating not morethan four lesions at a time and limit the total volume of liver treated to < 20- 30%.Patients with more than 40% of liver volume replaced with tumor are usually notcandidates for ablative therapy alone Non-resectional ablative strategies are par-ticularly attractive approaches for the treatment of many patients with HCC whohave limited functional hepatic reserve due to cirrhosis These techniques permitpinpoint tumor ablation while maximizing the preservation of normal liver In someinstances, ablative modalities may be used in conjunction with resective therapy totreat a “close” or “positive” margin of resection

Cryotherapy

The Physiology of Cryoinjury: Deep Freeze

The mechanism by which subzero temperatures destroy tumors are not tissuespecific Normal and neoplastic tissues are sensitive to exposure to extreme cold.The explanations for how cryotherapy results in cell death are multifactorial, and

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include both physical and chemical mechanisms depending upon the rate ofcooling Factors such as the depth of hypothermia, rate of decline in tempera-ture, and number of freeze-thaw cycles are all important variables in regards tothe percent of cell death achieved

When a cryoprobe is inserted into the liver, three overlapping zones of injurydevelop within the iceball The rate of freezing decreases in proportion to thedistance from the probe and creates zones of intermediate and slow cooling Simi-larly, a grading of temperature develops in the iceball, falling 3 to 10˚C per milli-meter (from -170˚C near the probe to just below the 0˚C at the periphery of thecryolesion) The dynamics of the freezing process cause different mechanisms ofinjury to occur in these three zones

Cooling Rates

Cooling rates affect the proportion of cells killed in a single freeze cycle Maximalcell death is achieved by using either slow or rapid cooling rates whereas greatest cellsurvival is seen with intermediate cooling rates Cellular dehydration causes the lethalinjuries when slow cooling rates are used, while rapidly cooled cells are destroyed by themechanical action of ice crystallization

Intra- and extracellular fluids are complex solutions containing varying amounts ofprotein, macromolecules and electrolytes The presence of these solutes depresses thefreezing point of water and allows it to supra-cool rather than crystallize below 0˚C.Because of differences in the composition of the intra- and extracellular compartments,the extracellular fluid freezes before the intracellular fluid As ice forms within theextracellular space, solutes are excluded leaving a hyperosmotic extracellular environ-ment Cellular dehydration occurs as the unfrozen intracellular water flows out of a cellalong the osmotic gradient As a consequence of cellular dehydration, the intracellular

pH and ion concentrations are altered, proteins denature and membrane bound zyme systems are destroyed Although many cells die as a direct result of dehydration,others succumb to isotonic rehydration during the thaw cycle When the cryolesionthaws, the extracellular fluid thaws first creating a relatively hypotonic environment.Water flows into the hyperosmolar and hypertonic cells causing them to burst Thistype of injury predominates in the slowly cooled zone at the periphery of the cryolesion

en-In contrast, rapidly frozen tissue is destroyed by an altogether different nism Cooling rates on the order of 50˚C per minute cause intracellular fluid tofreeze before cellular dehydration takes place Intracellular ice is particularly le-thal Small ice crystals coalesce, resulting in a physical grinding action that dis-rupts cellular organelles and membranes leading to reproducible and certain celldeath This type of cooling is present only in close proximity to the cryoprobe.With intermediate cooling rates (1-10˚C per minute), the cells dehydrate and theextracellular fluid turns to ice However, the temperature falls fast enough to freeze theintracellular water before cellular dehydration reaches a critical level Intracellular iceformation excludes solute, thereby increasing intracellular osmotic concentration, equal-izing the osmotic gradient, and preventing further cellular dehydration In this setting,the critical level of dehydration allowing influx of solute is not reached, thus protectingthe cell from the lethal injury caused by water influx during the thaw cycle Cells in thezones of intermediate cooling therefore have improved survival, and several freeze-thaw cycles are necessary to effect complete cell death

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Hypothermia and the Thawing Process

The sensitivity of different tissues to hypothermia varies considerably Most mal hepatocytes exposed to temperatures below –15 to -20˚C die, whereas nearly allhepatocytes cooled to -10˚C survive Bile ducts, connective tissue and vascular struc-tures tolerate lower temperatures than hepatocytes Unfortunately, liver tumors areeven more robust than normal hepatocytes and tend to require even deeper hypoth-ermia for complete and certain destruction As a general rule, a temperature of lessthan -40˚C is sought In practice, assuring that all tumor cells reach this temperaturerequires the iceball to extend at least 1 cm beyond the temporal edge of the tumor.Additional tissue damage occurs during the thawing from the process ofrecrystalization In brief, as the tissue warms ice crystals reform, coalesce and en-large, mechanically disrupting the cellular membrane at temperatures of –20˚ to –25˚C Permitting slow and passive re-warming augments these effects

nor-Although tissue in closest proximity to the cryoprobe may be adequately ablated

in one freeze/thaw cycle, multiple cycles are necessary to ensure that tumor cells atthe periphery reach the depth of hyperthermia required for reliable cell kill

Technical Aspects of Cryotherapy

Hepatic cryotherapy can be performed through a variety of approaches, ing the percutaneous, laparoscopic and open method The open approach allowsthe most flexibility and permits treatment of lesions not accessible by other meth-ods, albeit with increased operative morbidity Minimally invasive cryotherapy tech-niques should be limited to highly selected patients

re-or intraoperative complications A unique, but rare, complication of cryotherapythat must be anticipated is “cryoshock.” This complication is typically manifested

by profound systemic hypotension, pulmonary failure, renal failure, andcoagulopathies Renal failure can be minimized by aggressive intraoperative hydration.Hypothermia can be alleviated using heated fluid, airway circuits and a Bair Hugger™warming system, and any signs of excessive bleeding should be aggressively treatedwith appropriate blood products

Operative (Open) Approach

The abdomen may be approached through a subcostal, bilateral subcostal ron-type), or mid-line incision The peritoneal cavity is carefully inspected for anyevidence of extrahepatic metastases Enlarged lymph nodes, particularly those in thehepatoduodenal ligament, should be evaluated by frozen section The falciform liga-ment is divided up to the level of the hepatic veins to permit careful bimanualpalpation A 5 MHz intraoperative ultrasound transducer is used to evaluate each seg-ment of the liver systematically to determine the extent of disease and its relationship

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to the vascular and biliary structures All lesions seen on preoperative studies should

be confirmed by intraoperative ultrasound and/or biopsy

Once an intraoperative strategy is defined, a Penrose drain or vessel loop is placedaround the porta hepatis should inflow occlusion be required later The cryoprobe isintroduced into the center of each lesion under ultrasound guidance The place-ment is confirmed sonographically by viewing the probe in two or three perpen-dicular planes When at all possible, the cryoprobe should be introduced throughthe anterior surface of the liver By placing the ultrasound transducer on the poste-rior surface of the liver, the introduction of the cryoprobe and the subsequent for-mation of the ice ball can be carefully monitored In order to minimize tumor spillageand to avoid “cracking” the surface of the tumor, the probe should ideally be in-serted through normal liver before entering the tumor Direct introduction of theprobe into the tumor or a wire-guided Seldinger-style localization may be used de-pending upon the depth of the lesion The Seldinger technique is preferred for deepintraparenchymal and poorly palpable tumors After identification of the tumor byintraoperative ultrasound, an echogenic needle is passed into the center of the lesionand is subsequently exchanged for a J-wire Once the J-wire is in place, the tract isdilated with a coaxial dilator and peel away sheath The dilator is withdrawn afterproper position is established and the cryoprobe is inserted through the sheath intothe center of the tumor The correct positioning of the cryoprobe should be re-evaluated in two or three different axes Ideally the probe is placed through thetumor with the tip near the opposite margin

The size and location of the tumor governs the type of cryoprobe used Thesurgeon must be familiar with the physiology of cryotherapy in order to determinewhich shape of probe is most suitable for the situation The most commonly usedcryo-system employs vacuum insulated probes and supra-cooled liquid nitrogen re-frigerant Probes of various sizes and shapes are utilized to achieve the desired results(Fig 18.1) A 3 mm blunted probe creates a lesion up to 4 cm in diameter, while an

8 mm trocar probe creates a freeze zone up to 6 cm Probes may be used in tandem

to create larger lesions Flat-faced probes which form a “half-moon” lesion may beapplied directly to the surface of the liver to form lesions 3 to 4 cm in size.Once the cryoprobe is positioned, great care must be taken to insulate the sur-rounding tissue Laparotomy sponges are usually sufficient for this purpose Thefreezing process then commences At -100˚C, the cryoprobe becomes stuck in thehepatic parenchyma, and additional probes may be safely placed When one is justbeginning to perform cryotherapy we recommend using one probe at a time inorder to ensure adequate monitoring of the cryoablation and reduce the risk ofintraoperative hypothermia The freeze front appears as a hyperechoic rim with pos-terior acoustic shadowing on intraoperative sonography (Fig.18.2) Cooling contin-ues until the freeze front extends 1 cm beyond the margin of the tumor This processusually takes 8 to 15 minutes to complete depending upon the efficiency of thecryosystem and the size of the tumor

Following completion of the first freeze cycle, the tissue is thawed passively plete thawing may take up to 20 to 30 minutes Since cryotherapy failure usuallyoccurs at the periphery of the ice ball, we recommend thawing only the most periph-eral centimeter before initiating the second freeze cycle This technique reduces opera-