We present a case of profound shock and lactic acidemia occurring in the context of a cryoablative procedure for hepatocellular carcinoma. After out ruling more common possible etiologies, we diagnosed our patient as having a rare cause of shock, unique to these types of cryoablative procedures, known as cryoshock. Cryoablation can result in multiple complications one of which is 'cryoshock', a life-threatening syndrome of multiorgan failure and coagulopathy that carries a high mortality, up to 40%. While the mechanism of cryoshock has not been completely elucidated, it appears to be mediated by the release of cytokines TNF-alpha, IL-1, and IL-6. It is causally associated with complete thaw prior to refreezing and double freeze cycles, as well as volume of and duration of cryotherapy. Cryoreaction, which is a milder phenomenon including chills fever, tachycardia, tachypnea and temporary renal damage has been described after 1% of cryoablation sessions. Reports of the management of cryoshock are scarce and the mainstay of treatment is organ support. While cryoshock has been described in radiology and surgical literature it has not previously been described in anesthesiology literature. We highlight this as a potential serious complication which should be considered by all clinicians involved in these cases.

Cryotherapy has been used clinically in the treatment of metastatic liver malignancies since the 1980s. Rapid freezing to sub-zero temperatures promotes ice formation in the extracellular space and the exit of intracellular water. Cellular death is the result of dehydration, protein denaturation, and microcirculatory failure. Cryotherapy probes use nitrogen or argon gas as a coolant and the development of the ice ball can be monitored using ultrasound, computed tomography, or magnetic resonance imaging. Traditionally, cryotherapy has been performed during laparoscopy or laparotomy, using intraoperative ultrasound for image guidance. A decrease in cryoprobe size (from ~24 Fr to ~15 gauge) in conjunction with experience gained in open cryosurgical treatment has allowed the development of minimally invasive percutaneous approaches. In this review, we describe the use of cryotherapy for treatment of primary or secondary liver neoplasms using a percutaneous approach.

Ablation of liver tumors is part of a multimodality liver-directed strategy in the treatment of various tumors. The goal of ablation is complete tumor destruction, and ultimately improvement of quality and quantity of life for the patient. Technology is evolving rapidly, with important improvements in efficacy. The current state of ablation technology and indications for ablation are described in this review.

While there is promising survival data for cryosurgery of colorectal liver metastases, local recurrence following cryoablation remains a problem. We aimed to compare morbidity and mortality, as well as the recurrence pattern and survival after liver resection and cryotherapy (alone or in combination with resection) for liver metastases.

Between 1996 and 2002, 168 patients underwent liver resection alone and 55 patients had cryotherapy (25 in combination with liver resection) for colorectal liver metastases. The patient, tumour and operative details were recorded prospectively and the two patient groups were compared regarding morbidity, survival and recurrence.

More patients had a prior liver resection, liver metastases were smaller and less frequently synchronous, morbidity was significantly lower and hepatic recurrence was significantly more frequent in the cryotherapy group. Five-year survival rates following resection and cryotherapy were comparable (23 and 26% respectively), while overall and hepatic recurrence-free survival was inferior following cryotherapy.

Cryotherapy is a valuable treatment option for some patients with non-resectable colorectal liver metastases. While survival is comparable to that after resection, higher hepatic recurrence rates following cryotherapy should caution against the use of cryotherapy for resectable disease until the results of randomized controlled trials are available.

We aimed to assess the temperature distribution in the cryolesion during hepatic cryotherapy and the association with postoperative histological changes to optimise the technique and allow better preoperative planning. Hepatic cryolesions were produced in 22 pigs following laparotomy using a CMS-cryosystem and 8mm-AccuProbe-Cryoprobes. The temperature was measured in 1 min intervals at different distances from the probe during freezing. The animals were treated in 5 groups: (i) single freezing of 20 min; (ii) double freezing of 20 min each; (iii) single freezing of 40 min; (iv) single freezing of 20 min (n=4), histology at 1 week p.o., and (v) single freezing of 20 min and Pringle manoeuvre; [(i)-(iii) and (v): histology at 24 h p.o.]. The mean diameter of the -38 degrees C isotherm, i.e., the zone of effective treatment for colorectal metastases was 37 mm for group (i) with a mean iceball diameter of 59 mm and about 46 mm for groups (ii, iii, and v) with mean iceball diameters of 78, 75, and 75 mm, respectively. At 7 days postoperatively secondary necrosis was seen in the largest central part of the lesion, wherever temperatures of -15 degrees C or lower were achieved during cryosurgery. Under the hypothesis that -38 degrees C is the effective temperature for the destruction of colorectal liver metastases, a lesion of 37-mm diameter may be effectively treated with a single 8mm-AccuProbe-Cryoprobe and a 20 min single freeze cycle and a lesion of 46 mm may be effectively treated when a double freeze-thaw cycle of 20 min each, a single freeze cycle of 40 min, or a 20 min single freeze cycle with additional Pringle manoeuvre is used, when it is perfectly placed in the lesion.

The management of primary and secondary malignant liver tumors poses a great challenge to clinicians. Although surgical resection is the gold-standard treatment, most patients have unresectable malignant liver tumors. Over the past decade, various modalities of loco-regional therapy have gained much interest. Among them, thermal ablative therapy, including cryotherapy, microwave coagulation, interstitial laser therapy, and radiofrequency ablation (RFA), have been proven to be safe and effective. Despite the effective tumor eradication achieved within cryotherapy, the underlying freeze/thaw mechanism has resulted in serious complications that include bleeding from liver cracking and the 'cryoshock' phenomenon. Thermal ablation using microwave and laser therapy for malignant liver tumors is curative and is associated with minimal complications. However, this treatment modality is effective only for tumors <3 cm diameter. Radiofrequency ablation seems to be the most promising form of thermal ablative therapy in terms of a lower complication rate and a larger volume of ablation. However, its use is restricted by the difficulty encountered when using imaging studies to monitor the areas of ablation during and after the procedure. Moreover, the techniques of RFA need to be refined in order to achieve the same oncological radicality of malignant liver tumors as achieved by surgical resection. As each of the loco-regional therapies has its own advantages and limitations, a multidisciplinary approach using a combination of therapies will be the future trend for the management of malignant liver tumors.

To evaluate the complications from laser-induced thermotherapy (LITT) of malignant liver tumors and demonstrate that LITT is safe as an outpatient procedure.

During 8 years, 899 patients with malignant liver tumors were treated with magnetic resonance (MR) imaging-guided LITT. A total of 2,132 LITT procedures were performed to treat 2,520 lesions. To account for the technical evolution of LITT during this time and the change from performing the procedure on an inpatient basis to performing it on an outpatient basis, patients were assigned to four groups. Overall complication rates and major and minor complications in the inpatient versus outpatient groups were evaluated. Multidimensional contingency table analysis with the chi(2) test was performed.

On the basis of a total of 2,132 LITT procedures performed, complications were divided into major and minor categories and detected at clinical or imaging studies. Major complications included three deaths (0.1%) within 30 days after LITT, pleural effusion requiring thoracentesis in 16 (0.8%) cases, hepatic abscess requiring drainage in 15 (0.7%) cases, bile duct injury in four (0.2%) cases, segmental infarction in three (0.1%) cases, and hemorrhage requiring transfusion in one (0.05%) case. Minor complications included postprocedural fever in 710 (33.3%), pleural effusion not requiring thoracentesis in 155 (7.3%), subcapsular hematoma in 69 (3.2%), subcutaneous hematoma in 24 (1.1%), pneumothorax in seven (0.3%), and hemorrhage in two (0.1%) cases. Outpatient management did not significantly affect pleural effusion (P =.96) or subcapsular hematoma (P =.33) rate.

MR imaging-guided LITT with local anesthesia is safe and yields an acceptably low rate of major complications.

This paper reports a 7-year experience of cryoablation for colorectal and non-colorectal liver metastases.

A retrospective review was undertaken of patients treated in two adjacent UK centres in the north-west of England.

Over a 7-year period (1993-2000), 57 patients underwent cryotherapy for malignant hepatic tumours (41 colorectal, 16 non-colorectal). In the patients with colorectal metastases, preoperative carcinoembryonic antigen (CEA) levels fell significantly, from a mean of 444.1 to 6.22 micro g/l (P = 0.002). One patient died, two developed cryoshock and six had cardiorespiratory complications. All patients with colorectal metastases subsequently received 5-fluorouracil-based chemotherapy. The remaining 16 patients with non-colorectal tumours (seven neuroendocrine metastases, five hepatocellular carcinomas, three sarcomas, one cholangiocarcinoma) all received cryotherapy alone, with no major complications. The median survival for patients with non-colorectal metastases was 37 months, compared with 22 months for those with colorectal metastases (P = 0.005).

Hepatic cryotherapy is effective and safe, as demonstrated by the significant reduction in postoperative CEA concentration and the low risk of complications. However, this initial short-term success was not reflected in 5-year survival rates. Cryotherapy for non-colorectal metastases had a greater long-term survival benefit and is a useful means of controlling symptoms.

In this article, the author reviews the recent advances in the surgical management of hepatocellular carcinoma (HCC). Partial hepatic resection or, in some instances, liver transplantation provides the best chance for cure. Risk of perioperative mortality after partial hepatectomy is less than 5% in most experienced centers. Careful preoperative assessment of hepatic function is important to reduce the risk of postoperative liver failure after liver resection. Long-term outcomes after resection are comparable to those with liver transplantation, with reported 5-year survival rates of 25%-50%. Although limited controlled comparative studies exist, surgical and nonsurgical local ablative therapies, including ethanol and radiofrequency ablation, may result in survival benefit.

Radiofrequency (RF) ablation is an interstitial focal ablative therapy that can be used in a percutaneous fashion and permits in situ destruction of hepatic tumors. However, local tumor recurrence rates after RF ablative therapy are as high as 34% to 55%, which may be due in part to the inability to monitor accurately temperature profiles in the tissue being ablated, and to visualize the subsequent zone of necrosis (thermal lesion) formed. The goal of the work described in this paper was to investigate methods for the real-time and in vivo monitoring of the spatial distribution of heating and temperature elevation to achieve better control of the degree of tissue damage during RF ablation therapy. Temperature estimates are obtained using a cross-correlation algorithm applied to RF ultrasound (US) echo signal data acquired at discrete intervals during heating. These temperature maps were used to display the initial temperature rise and to continuously update a thermal map of the treated region. Temperature monitoring is currently performed using thermosensors on the prongs (tines) of the RF ablation probe. However, monitoring the spatial distribution of heating is necessary to control the degree of tissue damage produced.

For most patients with primary liver cancer surgical treatment is not feasible and prognosis without treatment is poor. We aimed to assess the morbidity and efficacy of transarterial chemoembolization (TACE) with lipiodol and mitomycin C in these patients in a prospective case-control study.

From August 1996 to May 2000 22 patients with non-resectable hepatocellular carcinoma were treated with TACE. In case of radiological or tumour-marker response, treatment was repeated after 4--6 weeks, up to seven times per patient.

Morbidity was 23% and usually minor, no patient died within 30 days of treatment. A decrease in size of the reference tumour or constant tumour-size in CT-scan were observed in 14 of 20 patients (70%) and of the 19 patients with elevated AFP-serum levels 12 (63%) had an AFP reduction following treatment. The median survival time was 14 months with a 1- and 2-year survival rate of 69% and 29%, respectively. Survival was not different in radiological or AFP responders vs non-responders.

While TACE with lipiodol and mitomycin C for primary liver cancer is associated with considerable antitumoural efficacy, as demonstrated by tumour marker and radiological response, an effect on patient survival is not evident. New treatment options with an impact on survival are needed for these patients.

Primary hepatocellular cancer is a disease with a poor prognosis for which there is little consensus on treatment and a paucity of comparative trials. The coexistence of cancer with cirrhosis complicates treatment, and also confers a high risk for the development of further tumours. Surgery, either by hepatic resection or orthotopic liver transplantation, is only a feasible option in a minority of patients. This article surveys the non-surgical approaches to the treatment of hepatocellular cancers-local ablation techniques, arterial embolization with and without chemotherapy, conventional chemotherapy and hormonal modulation, and targeted and external irradiation.

Most cirrhotic patients with hepatocellular carcinoma (HCC) are not candidates for resection. Transarterial chemoembolization (TACE) may ablate a significant portion of the tumor but has a high rate of recurrence. Cryosurgery may permit successful ablation of hepatic tumors but can be complicated by postoperative hemorrhage and is also associated with a significant risk of recurrence. The combination of the two techniques might be beneficial. We evaluated in a prospective study the safety and efficacy of this combination in cirrhotic patients with unresectable HCC. Fifteen patients were included in this study. All but one patient underwent one or several sessions of TACE before cryosurgery. Cryoablation was successfully performed in each patient. The patient who did not undergo preoperative TACE required reoperation for hemorrhage. Another patient with Child-Pugh class B cirrhosis died postoperatively of hepatic and multiorgan failure. At a mean follow-up of 2.5 years, three patients had recurrence of disease, and 13 of 15 patients were alive with the longest survival time being 5 years. The actuarial survival rate at 5 years was 79%. Cryosurgery after TACE is feasible in cirrhotic livers with HCC and can increase the cure rate in large tumors. TACE may reduce the risk of hemorrhage after cryosurgery but can increase the risk of hepatic failure in patients with poor hepatic function.

Despite continuing research and the development of alternate therapeutic options, prostate cancer remains problematic. Chemotherapy has played a minor role as a treatment option due to its lack of efficacy. Whereas cryotherapy has received renewed attention as a treatment modality, it too fails to offer an absolute curative option. Previously, we reported on the utilization of a therapeutic model, which, in combination, increases cell death in a canine renal cell model. Based upon that study, we investigated a combination therapy model as an alternative for the treatment modality for prostate cancer. We hypothesized that the combination of chemotherapy and cryosurgery would result in enhanced cell death, thereby presenting a more effective treatment of prostate cancer. A human prostate cancer cell (PC-3) model was exposed to 5-fluorouracil (5-FU) for 2 and 4 days (prefreeze), freezing (-5 to -100 degrees C), or a combination of the two treatments, and each was assessed for effectiveness over a 2-week posttreatment period. Additionally, investigation into the mechanisms of cell death initiated by the respective therapies was performed through DNA cleavage analysis. For chemotherapy, cultures exposed to 5-FU (2-4 days) yielded a 15-25% loss in cell survival. For cryotherapy, cultures exposed to a temperature window of -5 to -20 degrees C yielded an initial 5-70% loss of viability but cells propagated over time. Cultures exposed to temperatures of -25 to -80 degrees C yielded a 90-99% (+/-4.5%) initial loss in viability with repopulation observed by 12 days postthaw. Cells frozen to -100 degrees C yielded 100% (+/-0.3%) loss of viability and exhibited no signs of propagation. For chemo-cryo therapy, combination treatment at milder temperatures (-5 to -25 degrees C) resulted in an enhanced loss of cell viability compared to that for either treatment alone. Combination treatment at lower temperatures (-40 to -80 degrees C) resulted in a complete loss of cell viability. DNA fragmentation analysis at 48 h posttreatment revealed that dead (detached) cells treated with 5-FU died primarily through apoptosis, whereas dead cells from freezing (-15 degrees C) alone died primarily through freeze-rupture and necrosis. Detached cell analysis from combination treatment at -15 degrees C revealed the presence of apoptotic, necrotic, and freeze-rupture cell death. Scanning electron micrographs of cells exposed to freezing contributing to cell death. These data demonstrate that the combination of 5-FU at sublethal doses and freezing temperatures improves human prostate cancer cell death efficacy. Further, we suggest that chemo-cryo therapy offers a potential alternative treatment for the control and eradication of prostate cancer.

Cryosurgical ablation (CSA) is an established treatment for primary and metastatic liver malignancies. The study objective was to qualitatively define our patient CSA experience and compare it with the existing literature.A retrospective review was conducted of patients who underwent isolated CSA from September 1995 to April 2000. Data were collected on patient characteristics, tumor characteristics, sequential 12-hour laboratory data, transfusion requirements, and survival data. SPSS 9.0 (SPSS, Chicago, Illinois) was used for data analysis.Twenty-four patients (14 men, 10 women) were studied. Eighty-seven lesions (mean 3.8/patient) were treated. Six patients underwent treatment for primary liver tumors, whereas 16 were treated for metastatic disease. White blood cell count increased 1.7-fold, and platelet count decreased 2.0-fold. Aspartate aminotransferase and alanine aminotransferase increased significantly 42- and 29-fold, respectively. Seven out of 21 (33%) patients required blood transfusion. Our overall complication rate was 25%. Perioperative mortality was 0%. Kaplan-Meier survival analysis revealed an overall survival of 46% at a median follow-up of 33.7 +/- 6.8 months.CONCLUSIONS:Although isolated CSA of hepatic malignancies results in major and minor alterations in serologic parameters, they equate to little clinical significance. Blood product transfusions are necessary in 30% patients post-CSA. Significant perioperative complications occur in 25% of patients. Survival estimates suggest that nearly 50% of patients undergoing CSA can be expected to survive longer than 2 years post-CSA.

The purpose of this study was to evaluate the feasibility of MR-guided percutaneous cryotherapy of the porcine liver and to correlate the resulting tissue necrosis with MR imaging and histology. Using an MR-compatible, argon-based cryotherapy system (CryoHit; Galil Medical Ltd., Israel) with 2- and 3-mm diameter tapered cryotherapy probes, MR-guided percutaneous cryotherapy was performed in seven pigs (mean body weight, 40 kg) under general anesthesia in a short-bore magnet (1.5 T ACS NT; Philips, The Netherlands) using an ultrafast T2-weighted single-shot LoLo TSE sequence and a T1-weighted gradient-echo sequence. The frozen liver tissue was depicted accurately on fast T2- and T1-weighted sequences, providing precise delineation of the ablated tissue volume. On follow-up postcontrast MR controls, the cryolesions appeared avascular. They decreased in size compared with the initially frozen volume down to 70% at a 2-week follow-up. Histologically, a coagulation necrosis with a close correlation to the MR follow-up examinations was objectified. No cryotherapy-related complications occurred. J. Magn. Reson. Imaging 2001;13:50-56.

The objective of this study was to compare CT and sonography for monitoring radiofrequency (RF) lesions in porcine livers.

RF lesions (n = 12) were created in three pig livers by applying 13 min of current to a multielectrode RF probe with a target temperature of 95 degrees C. Helical unenhanced CT and corresponding axial sonography were performed before ablation, at 2 min, 8 min, and immediately after ablation. Contrast-enhanced CT was performed after ablation. CT scans and sonograms were evaluated by blinded observers for conspicuity of the RF lesion, edge detection (visibility of liver-lesion interface), and artifacts. Hounsfield units were recorded at every time interval, and radiologic-pathologic correlation for lesion size and configuration was performed.

Mean size of RF lesions was 3. 03 +/- 0.9 cm. On CT, RF lesions had consistently lower attenuation values than surrounding liver (22.2 H lower than liver at 8 min, p < 0.0001). Echogenicity was variable with sonography (hypoechoic = 59%, hyperechoic = 25%, isoechoic = 16%). Unenhanced CT significantly improved conspicuity, edge detection of RF lesions, and decreased artifacts compared with sonography (p < 0.05). Contrast-enhanced CT improved RF lesion detection, border discrimination, and artifacts compared with sonography (p < 0.05). Unenhanced CT had the best correlation to pathologic size (r = 0.74), followed by contrast-enhanced CT (r = 0.72) and sonography (r = 0.56). Contrast-enhanced CT best correlated with lesion shape, but slightly overestimated size because of areas of ischemia peripheral to the RF lesion.

In this animal model, unenhanced CT was an effective way to monitor RF ablation compared with sonography because of increased lesion discrimination, reproducible decreased attenuation during ablation, and improved correlation to pathologic size.

Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide. Recent surveillance programs have allowed early detection and diagnosis, but overall survival of patients with HCC remains poor. This article provides a definition for localized HCC and summarizes the array of treatments that have emerged and the salient literature and findings for each. Among the treatments reviewed here are surgical resection, orthotopic liver transplantation, and local ablative therapies such as cryosurgery, percutaneous ethanol injection therapy, and transarterial chemoembolization.

Since microvascular dysfunction with complete circulatory arrest and, thus, prolongation of tissue ischaemia is considered a potential mechanism for cell necrosis following hepatic cryosurgery, we determined the temperature necessary for induction of complete nutritive perfusion failure in cryothermia-treated rat livers. After localization of the cryoprobe with seven thermocouples and application of a single or double freeze-thaw cycle, in vivo fluorescence microscopy of the cryoinjured left lobe was performed over a 2-h period using a computer-controlled stepping motor, which guaranteed analysis of the identical liver tissue segments with exact allocation of the thermocouples and thus determination of tissue temperature. Cryothermia resulted in a central non-perfused part of injury, surrounded by a heterogeneously perfused peripheral zone. The non-perfused area after single and double freezing continuously increased over the first 90-min period due to a successive shutdown of perfusion within the peripheral border zone. Analysis of the thermocouples' temperature at the end of freezing revealed the 0 degrees C-front at 11.7 mm (single freeze-thaw cycle) and 12.1 mm (double freeze-thaw cycle) distant from the centre of the cryoprobe, which exactly corresponds with the initial (30 min) expansion of the area with nutritive perfusion failure. The increased non-perfused tissue area at 2 h conformed a critical border temperature between 8.29 +/- 1.63 degrees C and 9.07 +/- 0.24 degrees C. From these findings, we conclude that freezing of liver tissue to temperatures of at least < 0 degrees C causes complete/irreversible perfusion failure, which consequently will result in cell death and tissue necrosis, and may thus be supposed as a prerequisite for the safe and successful application of cryosurgery in hepatic tumour ablation.

Percutaneous ethanol injection (PEI) and cryosurgery are increasingly used for the treatment of liver malignancies. To create a safety margin and to destroy completely diffusely growing tumors, the precise destruction of healthy liver tissue is necessary. Little is known about the effects of operating on this type of tissue. This study evaluated the effects and side effects of PEI and cryosurgery when applied to normal parenchyma of the liver.

Two groups of six minipigs each were treated with either PEI or cryosurgery to create necrosis in the liver. During and after the procedures, vital signs were monitored and necrotic areas were observed by ultrasonography. Standard and immunohistochemistry stains were made from samples of the necrosis, the liver, and the lung.

In the PEI group, thromboembolic complications occurred in all animals (fatality rate 50%). Hematogenous spread of hepatocytes was demonstrated by immunohistochemistry and was a cause of pulmonary embolism. In the cryosurgery group, neither specific complications nor signs of cell spillage occurred. Because of an isolating effect of blood perfusion, hepatocytes close to the portal triads were less damaged, vital cells were present in the periphery, and the necroses were smaller than the induced lesions.

The effect of PEI in healthy liver tissue is unpredictable. This makes the creation of a safety margin or the treatment of a diffusely infiltrating tumor impossible. PEI always introduces the risk of hematogenous cell spread. Effects of cryosurgery are less dependent on tissue qualities. In both techniques, the real extent of complete tissue destruction cannot be visualized by ultrasonography.

Liver metastases, especially from colorectal primary cancers, are treatable and potentially curable. Imaging techniques such as CT, MRI, and sonography have advanced in recent years and led to increased sensitivity and specificity in the diagnosis of liver metastases. Liver surgery also has been revolutionized in the past two decades. Dissections along nonanatomic lines have permitted the resection of multiple lesions that previously might have been considered unresectable. We regard resection of a solitary hepatic metastasis or up to four metastases from colorectal carcinoma as the best treatment for this condition. In patients over 70 years of age and those with medical conditions preventing surgery, we endorse expectant follow-up as long as the tumor remains stable. But if the tumor begins growing rapidly and local techniques cannot be used, we consider systemic chemotherapy. In patients with progressive metastatic liver disease, we initiate systemic therapy or hepatic arterial infusion. In young patients with metastatic disease, even when the disease is indolent or symptomatic, it may be difficult not to treat. We use either local regional therapy (resection or regional infusion) or systemic chemotherapy followed by regional therapy. In patients with neuroendocrine tumors metastatic to the liver, the first approach we use is not to treat because there may be a long period of stable disease. We use Sandostatin (Sandoz Pharmaceuticals, East Hanover, NJ) to treat symptoms. If the tumor progresses and symptoms cannot be controlled, these vascular tumors can be treated by embolization or chemoembolization, with high expectations of response. Newer approaches to liver metastases such as cryosurgery, chemoembolization, and interstitial radiation are also available. Cryosurgery is an ablative procedure that has not been proven yet to be as effective as surgical removal of metastases. However, in a situation where surgery cannot be performed, cryosurgery is an alternative. Chemoembolism has not been proven to be more effective than systemic therapy for liver metastases, but it allows another regional approach. External localized radiation can be used for patients who fail first-line treatment or in new protocols to delineate its value, perhaps in concert with chemotherapy. We also consider offering external localized radiation in patients who fail first-line treatment, perhaps in concert with chemotherapy. The usefulness of these techniques compared with surgery or regional therapy is being investigated.

Cryosurgery for liver metastases may improve survival for unresectable hepatic metastases. The laparoscopic approach to managing these tumors is a novel method fostered by increasing surgeon and patient interest in minimally invasive surgical techniques and the development of laparoscopic ultrasound and cryoprobes. A retrospective review of our patients who underwent laparoscopic cryoablation of hepatic tumors from April 1996 to December 1997 was conducted. We report on this experience and comment on the feasibility and safety of the procedure based on this early trial.

Between 1 Jan 1996 and 1 Apr 1998 29 patients underwent cryosurgical therapy for liver metastasis at the Department of Surgery at the University of Mainz.

No complications occurred following cryosurgery alone (n = 12). Within the group of patients with a combined procedure (n = 11) 1 patient had temporary liver failure and 1 patient died of sepsis. Following freezing of the cutting zone (n = 6) 1 patient showed a bile fistula and 1 ascites. In 15 cases of 28 dismissed patients with remaining destroyed tumor tissue the follow-up showed no tumor recurrence (median follow-up 11 months). On the other hand 9 patients had a tumor recurrence within the liver, 3 patients at extrahepatic regions and 7 patients developed a tumor recurrence within the freezing zone.

The objective of this study was to investigate the use of cryosurgery and to determine whether there is a role for combined therapy with alcohol ablation in the treatment of patients with hepatocellular carcinoma.

Twelve patients with biopsy proven hepatocellular carcinoma underwent ultrasound-guided cryosurgical ablation of their liver tumor. Postoperative alcohol ablation was performed on those patients who were found to have residual tumor or recurrence after the cryosurgical procedure.

Of the 12 patients (9 males, 3 females) the size of the primary tumor ranged from 3-13 cm with average size of 7 cm in greatest dimension. Most patients had advanced disease according to the TNM staging system: 9 patients had Stage IVA disease, 2 Stage III, and 1 Stage II. Three patients had residual tumors after the cryosurgical procedure. The residual tumor was treated with alcohol ablation. The 1-year survival rate for the entire group was 50% (5 of 10) and the 2-year survival rate was 30% (3 of 10). At last follow-up, 1 patient with an 8-cm tumor was disease free for 3 years and another patient with a 13-cm tumor was disease free for 2.5 years. Both of these patients had Stage IVA disease.

The authors found cryosurgery to be promising in the treatment of this extremely aggressive form of cancer, with the ability to prolong patient survival. Follow-up treatment with alcohol ablation is an important adjunct in treating residual tumor and controlling recurrences.

The objective of this study was to investigate the use of cryosurgery and to determine whether there is a role for combined therapy with alcohol ablation in the treatment of patients with hepatocellular carcinoma.

Twelve patients with biopsy proven hepatocellular carcinoma underwent ultrasound-guided cryosurgical ablation of their liver tumor. Postoperative alcohol ablation was performed on those patients who were found to have residual tumor or recurrence after the cryosurgical procedure.

Of the 12 patients (9 males, 3 females) the size of the primary tumor ranged from 3-13 cm with average size of 7 cm in greatest dimension. Most patients had advanced disease according to the TNM staging system: 9 patients had Stage IVA disease, 2 Stage III, and 1 Stage II. Three patients had residual tumors after the cryosurgical procedure. The residual tumor was treated with alcohol ablation. The 1-year survival rate for the entire group was 50% (5 of 10) and the 2-year survival rate was 30% (3 of 10). At last follow-up, 1 patient with an 8-cm tumor was disease free for 3 years and another patient with a 13-cm tumor was disease free for 2.5 years. Both of these patients had Stage IVA disease.

The authors found cryosurgery to be promising in the treatment of this extremely aggressive form of cancer, with the ability to prolong patient survival. Follow-up treatment with alcohol ablation is an important adjunct in treating residual tumor and controlling recurrences.

Cryosurgery may be considered for patients whose hepatic lesions are not amenable to surgical resection, i.e., patients with multiple hepatic lesions and/or lesions abutting major vascular structures. Because the size of the iceball created during the procedure can be carefully controlled, cryosurgery has the advantage of being a focal technique that spares much more noncancerous liver tissue than surgical resection. The major complications of hepatic cryosurgery are the same as those of hepatic resection: hemorrhage, pleural effusion, bile leak fistula, perihepatic abscess, and hepatic failure. In addition, there is a risk of coagulopathy when large tumors are frozen using multiple freeze-thaw cycles. In general, operative morbidity is related to the volume of frozen tissue, the number of freeze-thaw cycles, and number of cryoprobes. Further experience and accrual of long-term data should better define the indications for hepatic cryosurgery and minimize the incidence of complications.

Between November 1973 and December 1996, the in situ freezing of tumor, i.e., cryotherapy, was performed with liquid nitrogen (-196 degrees C) on 235 patients with primary liver cancer (PLC). There were no operative mortalities or severe complications. The 5-year survival was 39.8% for the 235 PLC patients, and 55.4% for the 80 patients with small PLC (< or = 5 cm). When analyzed with respect to treatment modalities without considering the size of the tumor, the 5-year survival was 26.9% for 78 PLC patients treated by cryotherapy alone; 39.6% for 58 PLC patients treated by cryotherapy plus hepatic artery ligation and perfusion; 46.0% for 27 PLC patients treated by cryotherapy for residual tumor plus resection of the main tumor; and 60.4% for 72 PLC patients treated by cryotherapy followed by resection of the frozen tumor. These results indicate that cryotherapy is a safe and effective treatment for PLC.

The use of freezing temperatures for the therapeutic destruction of tissue began in England in 1845-51 when James Arnott described the use of iced salt solutions (about-20 degrees C) to freeze advanced cancers in accessible sites, producing reduction in tumor size and amelioration of pain. Improved freezing techniques were possible early in the 1990s when solidified carbon dioxide came into use and later when liquid nitrogen and nitrous oxide became available. Nevertheless, cryotherapy was a minor technique, used only for the accessible lesions of skin and mucosa. With the development of modern cryosurgical apparatus by Cooper in 1961, a resurgence of interest in cryosurgery was initiated and techniques for diverse clinical conditions, including visceral cancer, evolved, After the initial widespread clinical trials matured in the 1970s, some applications of the technique fell into disuse while others became standard treatment. Late in the 1980s, further improvements in apparatus and imaging techniques have permitted increased clinical use in neoplastic disease, including visceral cancer.

There have been reports that suggest cryosurgical techniques may be a useful adjunct to surgical resection or even a viable alternative treatment for hepatobiliary malignancies. Our objective was to evaluate the clinical results following cryoablation in conjunction with surgical resection for advanced hepatic tumors.

Thirty-two consecutive procedures in 31 patients with advanced liver tumors treated with cryosurgical ablation were evaluated. Cryosurgery was applied: (1) to achieve a > 1-cm tumor-free margin when standard surgical margins were close (2) with or without standard surgical resection to manage multiple tumors (3) with hepatic arterial portocath placement to increase tumor response. Cryoablation was applied to 47 of 105 lesions--independently in 4 patients and in combination with hepatic resection in 28 procedures.

Cryoablation was used in 11 procedures because of close surgical margins. In 21 operations cryosurgery was used for primary ablation. In 17 of these 21 patients both cryosurgery and resection were used for different lesions; in 4 cryosurgery alone was used. Transient changes in hepatic enzymes, PT, PTT, and platelets were at maximum on Postoperative Days 1-3. Surgical mortality and morbidity rates were 6 and 60%, respectively. Coagulation abnormalities were common: at least 30% reduction in platelets occurred in all patients and greater than a 50% reduction occurred in 19 of 32 (59%). Twenty patients had a PT > 15 s and 6 of these 20 also had a platelet count < 50,000. Associated complications included one wound hematoma, two GI hemorrhages, one intracranial hemorrhage, and one hepatic hemorrhage from the cryosurgical site. The actuarial patient survivals were 90, 59, 33, and 22% at 6, 12, 24, and 36 months, respectively.

This report helps define the risks and results of cryosurgical ablation as a complement to surgical resection for advanced hepatobiliary tumors. Management of lesions contiguous to major blood vessels may include either the Pringle maneuver or total vascular isolation. Since these procedures can have significant morbidity, we urge cautious application of cryosurgery for advanced hepatobiliary tumors in selected otherwise unresectable patients.

In patients undergoing liver resection for colorectal liver metastases, a resection edge either involved by tumour or with the tumour extending to within 1 cm is associated with a high risk of liver recurrence and survival is reduced markedly.

Twenty-six patients underwent cryotherapy of the resection edge following liver resection for metastases from colorectal carcinoma with an involved or inadequate (less than 1 cm) resection margin.

At a median follow-up of 23 (range 1-47) months four patients were alive and disease free, and 21 had developed recurrence, of whom 13 had died. One patient died following surgery. Sixteen patients developed recurrences involving the liver, only five of which were at the resection margin.

Cryotherapy to involved or inadequate resection margins improves local disease control considerably. The use of resection edge cryotherapy might allow a greater proportion of patients with liver metastases to be usefully treated and help to avoid high-risk resections.

Cryosurgical ablation of malignant hepatic tumors is being increasingly used for definitive treatment of metastatic colorectal and primary hepatic tumors. The lack of tumor necrosis near vessels that results from inadequate freezing may contribute to local recurrence and thus limit the applications of this therapy. This study was designed to determine whether single-freeze cryoablation could cause necrosis of both the pervascular and intralesional hepatic parenchyma.

Ten pigs were treated with one 15-minute cycle of cryoablation. Five additional animals were treated with overlapping cryolesions to simulate a double freeze. After 24 hours, animals underwent reoperation with portal vein cannulation and infusion of formalin. Serial sectioning and hematoxylin and eosin staining of cryolesions were performed.

Complete cell death was visualized within all cryolesions. There was no difference between once or twice-frozen tissue. Vessels within or adjacent to cryolesions showed necrosis of hepatic tissue up to the vessel wall. No sections revealed incomplete necrosis of perivascular hepatic parenchyma.

Single-freeze cryoablation results in necrosis of intralesional hepatic parenchyma without added benefit from repeat freezing. Complete necrosis of the perivascular tissue suggests that cryosurgical ablation can effectively cause necrosis immediately adjacent to vessels without concerns of incomplete ablation resulting from the heat sink effect.

This project aimed to determine the adequacy and accuracy of high-intensity focused ultrasound (HIFU) for ablating experimental liver tumour, and to assess imaging methods for monitoring the therapeutic results. The rabbit liver pseudotumour model was established by injection of Freund's complete adjuvant into the liver; the animals then received HIFU therapy via laparotomy at the focal point of the beam (1.1 MHz, 500 W/cm2, 20 s). The rabbits were sacrificed at scheduled times after treatment and liver tumours were examined histologically. Sequential imaging of the liver tumour was performed before and after HIFU treatment. HIFU accurately destroyed the rabbit liver tumour and induced coagulation necrosis 24 h later. Sonographic imaging studies revealed that characteristic changes occurred. A hyperechoic mass turned to a hypoechoic lesion with no Doppler signal, and a high echogenic rim appeared 24 h after HIFU treatment, correlating well with the pathological changes of a sonoablated lesion. These results verify that HIFU has the power to ablate liver tumour quite adequately and accurately, and that sonography is useful for monitoring sonoablated liver tumour.

The technological advances which have caused renewed interest in cryosurgery are the development of intraoperative ultrasound to monitor the therapeutic process and the development of new cryosurgical equipment designed to use supercooled liquid nitrogen. The thin, highly efficient probes, available in several sizes, can be placed in diseased sites via endoscopy or percutaneously in minimally invasive procedures. The manner of use is to place the probe in the desired location in the diseased tissue with ultrasound guidance. If required by the size or location of the tumor, as many as five probes can be inserted and cooled to -195 degrees C simultaneously. The process of freezing is monitored by ultrasound which displays a hypoechoic (dark) image when the tissue if frozen. Rapid freezing, slow thawing, and repetition of the freeze/thaw cycle are standard features of technique. Clinical applications which have become common in the past 4 years include the treatment of prostatic cancer and liver tumors. The cases selected for cryosurgery are generally those for which no conventional treatment is possible. However, especially in prostatic cancer, the operative morbidity is so low and the results of therapy are sufficiently good in the short term to merit consideration of use in earlier stages of the disease. Diverse tumors in other sites, such as the brain, bronchus, bone, pancreas, kidney, and uterus, have also been treated in small numbers by cryosurgery. Judging from this experience, further expansion in the use of cryosurgical techniques seems certain.

Cryosurgery currently is being used clinically to treat tumors in internal organs such as the liver and prostate. Although performed at present under ultrasound monitoring, magnetic resonance imaging (MRI)-guidance of these procedures not only permits monitoring of the frozen region during cryosurgery but also makes it possible to determine the temperature distribution in the frozen region, which is not possible using ultrasound monitoring. A good estimate of the region of destruction in the tissue can be obtained from correlating the temperature distribution and the time course of the freezing with the image of the frozen region. Unfortunately, MR pulse sequence-based temperature determination techniques such as diffusion, relaxation time, and chemical shift cannot be used for measuring the temperature in the frozen region because the T2 of the frozen regions is so short that there is effectively no RF signal from the frozen region. This paper describes a numerical technique for determining the two dimensional temperature distribution in the frozen region during MR image-guided cryosurgery of normal liver in rabbits. The technique involves solving the energy equation numerically in the frozen region to determine the temperature distribution there. The boundary conditions needed to solve the equation are determined from MR images of the frozen tissue during cryosurgery and from the measured temperature of the cryoprobe. The calculated temperature in the frozen region is then correlated with the damaged region (cryolesion) determined from post mortem histologic evaluation.

The authors evaluate the results of cryosurgery in malignant liver tumors.

The outcome of primary or secondary liver tumors is poor when resection can not be achieved. Encouraging results of cryosurgery have been reported in unresectable liver tumors, but this treatment needs further evaluation of its efficacy in homogeneous groups of patients.

From 63 patients with malignant liver tumors with various histology treated by cryosurgery in a 2.5-year period, the authors evaluated the results of 34 patients with nonresectable hepatocellular carcinoma (9 patients) or nonresectable metastases from colorectal cancer (25 patients). Cryosurgery was used either as a single treatment (4 hepatocellular carcinomas, 5 metastases) or in association with liver resection (5 hepatocellular carcinomas, 20 metastases). Systemic chemotherapy was used routinely before surgery and after surgery.

There was no intraoperative mortality. Mortality within 2 months was 3% and was unrelated to the procedure. Postoperative morbidity consisted of one sterile fluid collection and one biliary fistula (8%). At a mean follow-up of 16 months, (range, 2-27) local recurrence rate was 0% for hepatocellular carcinoma and 44% for metastases. Cumulative survival at 24 months was 63% and 52%, respectively, with 6 patients (67%) and 5 patients (20%) currently disease free. In the group of patients with metastases, survival was related to the size of the treated tumor (p = 0.06) and the absence of residual disease (p = 0.03).

Cryosurgery is safe and increases the number of patients with unresectable liver malignancies in whom surgery can aim at eradicating the tumor. Local recurrence is observed more frequently for metastases than for hepatocellular carcinoma. The benefit in survival is related to the complete treatment of the tumoral disease.

This project aimed to determine the adequacy and accuracy of high-intensity focused ultrasound (HIFU) for ablating experimental liver tumour, and to assess imaging methods for monitoring the therapeutic results. The rabbit liver pseudotumour model was established by injection of Freund's complete adjuvant into the liver; the animals then received HIFU therapy via laparotomy at the focal point of the beam (1.1 MHz, 500 W/cm2, 20 s). The rabbits were sacrificed at scheduled times after treatment and liver tumours were examined histologically. Sequential imaging of the liver tumour was performed before and after HIFU treatment. HIFU accurately destroyed the rabbit liver tumour and induced coagulation necrosis 24 h later. Sonographic imaging studies revealed that characteristic changes occurred. A hyperechoic mass turned to a hypoechoic lesion with no Doppler signal, and a high echogenic rim appeared 24 h after HIFU treatment, correlating well with the pathological changes of a sonoablated lesion. These results verify that HIFU has the power to ablate liver tumour quite adequately and accurately, and that sonography is useful for monitoring sonoablated liver tumour.

BACKGROUND: Primary and metastatic tumors in the liver are difficult to treat. When surgical resection is not feasible, cryotherapy is one of the several alternative approaches. METHODS: The data on outcomes from hepatic resections are reviewed, and the rationale and techniques of performing cryosurgery for unresectable hepatic cancers are described. The literature is reviewed and combined with the experiences of the authors on cryosurgery for management of hepatic tumors. RESULTS: The indications and techniques for performing cryosurgery are now well established. The procedure is relatively safe, and long-term survival rates of over 20% may be achieved. CONCLUSIONS: While cryotherapy is effective for localized tumors in the liver, additional adjuvant approaches are required to control disease in the untreated liver. Endoscopic techniques may minimize patient morbidity.

Ultrasound-guided hepatic cryosurgery is a potential treatment option for select patients with unresectable tumors. Intraoperative placement of cryoprobes and monitoring of tumor freezing with ultrasonography produce complete remission in 22% to 29% of patients with unresectable metastatic colorectal tumors to the liver. Perioperative nurses should be knowledgeable about cryosurgical techniques and be prepared to participate in this innovative treatment modality to provide optimal care to surgical patients.

Two decades have gone by since the earlier trials of alpha-fetoprotein (AFP) screening for hepatocellular carcinoma (HCC) were conducted in Africa and China. It is accepted that early detection, diagnosis and treatment of HCC remains an important target to be achieved before a breakthrough appears on the primary prevention of HCC. In the present study, screening investigations were performed in a high risk population of HCC, defined as persons who had hepatitis, blood transfusions, a family history of HCC, and were hepatitis B virus carriers. Ultrasonography combined with AFP serosurvey was accepted as an effective screening procedure to detect small HCC. Early diagnosis of HCC was not difficult if tumour markers and medical imaging were combined. Early resection has been proven to prolong survival of patients with small HCC. Repeated intralesional ethanol injection is an alternative treatment to surgery, while transcatheter arterial embolization is a less effective alternative. Re-resection of subclinical recurrence after curative resection has proven of merit in prolonging survival even further. Resection of small HCC remains an important approach in getting long-term HCC survival and to improving 5-year survival rates. It is more effective than treatment of large HCC. Studies on the secondary prevention of HCC have stimulated research into tumour markers, the natural history and cellular origin of HCC and oncogenes. However, the issue of 'cost-effectiveness' remains to be evaluated.