3-3 Combination of Cryosurgery with Transarterial Chemoembolization (TACE) for Liver Cancer

ABSTRACT

Transarterial chemoembolization (TACE), by itself, is not associated with improved survival, however, can shrink the mass of liver cancer. Combination of TACE and cryosurgery is expected to yield better therapeutic efficacy. It is shown that sequential TACE-cryosurgery might improve outcomes for patients with liver cancer with a lower local recurrence rate at the ablation area and lower incidences of hepatic bleeding complications.

INTRODUCTION

Cryosurgery has been used for two decades for the treatment of many benign, malignant, and metastatic cancers. More specifically, hepatocellular carcinoma (HCC) has been successfully treated either with cryosurgery alone or in combination with resection. Transarterial chemoembolization (TACE), by itself, is not associated with improved survival when compared with untreated controls, however, it has been proven to shrink liver cancer masses. Sequential TACE-resection might improve outcomes for patients with large HCC. Therefore, the combination of TACE and cryosurgery is expected to yield better therapeutic efficacy.

INDICATION

The combination of cryosurgery with TACE is mainly adaptable for larger liver cancers, including primary and metastatic lesions.

TECHNIQUE

TACE

TACE was performed in an interventional radiology suite after cross-sectional images were reviewed. A vascular sheath was placed into the femoral artery, and a Mickaelson catheter was advanced into the celiac and superior mesenteric arteries. Contrast was injected during rapid-sequence radiographic imaging, and arterial branches supplying the tumor were located. Doxorubicin (50 mg) and Mitomycin (10 mg) were mixed with Lipiodol (4–15 ml), and the mixture was injected into the arterial branches until hemostasis was achieved. If no shrinkage occurred at 2 weeks, a second TACE was performed.

Cryosurgery

Cryosurgery is performed with open, laparoscopic, or percutaneous approaches under real-time ultrasound guidance.

CLINICAL DATA

Clavien evaluated the safety and efficacy of this combination in cirrhotic patients with unresectable HCC. Fifteen patients were included in this study. Cryoablation was successfully performed in all, with one case of hemorrhage requiring reoperation. At a mean follow-up of 2.5 years, 13 of 15 patients were alive, with the longest survival being 5 years (5-year survival rate 79%).

Qian reported 34 patients with confirmed hepatic carcinomas treated with TACE followed by cryosurgery. During follow-up (3–15 months), 41.1% were clinically cured, and 44% effectively treated.

Xu and colleagues at Fuda Cancer Hospital (2001–2006) studied 980 HCC patients; 660 received TACE before cryosurgery. In 310 patients treated sequentially versus 110 treated with cryosurgery alone, the survival outcomes were as follows:

Local recurrence rate: 11% (sequential) vs. 23% (cryo-alone).

COMPLICATIONS

Main complications: hepatic bleeding, liver rupture, liver failure, thrombocytopenia, clotting dysfunction, acute renal failure, and pneumonia. The overall rate was 24%, with 21% in the sequential group and 26% in the cryo-alone group.

DISCUSSION

TACE remains a key treatment for unresectable HCC, though alone it shows limited survival benefit. Combining TACE with local ablation methods like cryosurgery significantly improves survival and reduces recurrence. Sequential TACE-cryosurgery enhances tumor necrosis by reducing blood flow and improving freezing efficiency.

Studies and meta-analyses show that TACE plus ablation yields better results than monotherapy for both small and large HCC nodules. Moreover, TACE helps reduce perioperative bleeding and complications.

Temperature below -40°C is required for tumor ablation; thus, ice-balls larger than the target lesion are necessary. Tumor size influences success rates, with smaller tumors achieving higher ablation efficacy. TACE shrinks the mass, improving cryosurgical efficiency and safety. Vascular occlusion techniques (e.g., Pringle maneuver) can further enhance tissue destruction.

The use of TACE prior to cryosurgery may increase efficacy, decrease bleeding risk, and improve survival — especially for large or vascular-adjacent liver tumors. For patients with cirrhosis or reduced hepatic reserve, percutaneous cryosurgery is preferred over open procedures.

CONCLUSION

A combined approach involving TACE and percutaneous cryosurgery improves survival in liver cancer, particularly in larger tumors. TACE reduces tumor burden and bleeding risk while enhancing cryoablation efficacy. Sequential TACE-cryosurgery offers superior long-term outcomes compared to cryosurgery alone.

REFERENCES

1. Gage AA. History of cryosurgery. Sem Surg Oncol 1998;14:99–109.
2. Korpan NN. History of cryosurgery. Springer, 2001.
3. Zacarian S. Cryosurgery for Skin Cancer and Cutaneous Disorders. Mosby, 1985.
4. Crew KA, Kuhn JA, McCarty TM, et al. Cryosurgical ablation of hepatic tumors. Am J Surg 1997;174:614–618.
5. Lam CM, Yuen WK, Fan ST. Hepatic cryoablation for recurrent hepatocellular carcinoma. J Surg Oncol 1998;68:104–106.
6. Sheen AJ, Poston GJ, Sherlock DJ. Cryotherapeutic ablation of liver tumors. Brit J Surg 2002;89:1396–1401.
7. Groupe D’Etude et al. Lipiodol chemoembolization vs. conservative treatment for HCC. NEJM 1995;332:1256–1261.
8. Yu YQ et al. Experience with liver resection after hepatic arterial chemoembolization. Cancer 1993;71:62.
9. Clavien PA et al. Cryosurgery after chemoembolization in cirrhotic patients. J Gastrointest Surg 2002;6:95–101.
10. Qian GJ, Chen H, Wu MC. Percutaneous cryoablation after chemoembolization. Hepatobiliary Pancreat Dis Int 2003;2:520–524.
11. Xu KC et al. Combination of percutaneous cryoablation with TACE. TCRT 2007;6:459–460.
12. Trevisani F et al. Randomized trials on chemoembolization for HCC. J Clin Gastroenterol 2001;32:383–389.
13. Marelli L et al. TACE outcomes with combination therapies. Cancer Treat Rev 2006;32:594–606.
14. Kaibori M et al. Preoperative chemolipiodolization for HCC. Anticancer Res 2004;24:1929–1933.
15. Popken F et al. Comparison of iceball diameter and temperature. Cryobiology 2000;40:302–310.
16. Mala T et al. MRI-estimated 3D temperature in liver cryolesions. Cryobiology 2001;43:268–275.
17. Seifert JK et al. Hepatic cryotherapy model. Cryobiology 2003;47:214–226.
18. Seifert JK, Morris DL. Recurrence after cryosurgery for hepatic metastases. Br J Surg 1999;86:234–240.
19. Pearson AS et al. Cryoablation or radiofrequency ablation for hepatic malignancies. Am J Surg 1999;178:592–599.
20. Kollmar O et al. Advanced hepatic tissue destruction in cryosurgery. Cryobiology 2004;48:263–272.
21. Mala T et al. Hepatic vascular inflow occlusion and cryoablation. J Surg Res 2003;115:265–271.
22. Seifert JK, Morris D. World survey on cryotherapy complications. World J Surg 1999;23:109–114.
23. Sarantou T et al. Complications of hepatic cryosurgery. Sem Surg Oncol 1998;14:156–162.
24. Seo DD et al. Preoperative portal vein embolization vs TACE. Ann Surg Oncol 2007;14:3501–3509.