1. Сryodestruction technology in patients with unresectable primary and metastatic liver cancer and pancreatic cancer metastatic liver cancer and pancreatic cancer ChzhaoA.V., 1 Ionkin D.A., 1 Zhavoronkova O.I., 1 Chzhao A.V., 1 Ionkin D.A., 1 Zhavoronkova O.I., 1 Vetsheva N.N., 1 Kungurtsev S.V. 2 Vetsheva N.N., 1 Kungurtsev S.V. 2 1 Vishnevsky Institute of Surgery, Moscow, Russia 2 Innovative Company BIOMEDSTANDART, Moscow, Russia

2. “Cold surgery” has a very long way. Treatment by freezing was known in ancient China, Rome, Greece. One can read about this kind of treatment in works of Hippocratis. Cold for cancer was first reported by James Arnott in England in 1850. Results of experimental study with liquid nitrogen was first reported by A. White in 1889. The first successful cryolysis for adenoma of prostate in Russia was reported by Freidovich A.I. in 1968. HISTORY.

3. TechniqueLocal reccurence (%) Overal reccurence (%) SurvivalMajor complications (%) 1- year 3- year 5- year Cryotherapy12-3978-8884371729 Microwave5-1350-787330167 Radiofrequency10-3147-868536246 Medline, Cochrane Collaboration Library, NLM, ClinicalTrials.gov. (01.1994-01.2010) * Cryoablation of unresectable Colorectal Liver metastases * (R. Jones, J. Tang, S. Pathak et al. Systematic review of ablation therapies for the treatment of unresectable colorectal liver metastases. // HPB. 2011. 13 (Suppl.2):83-84.)

4. Survival (%)Median survival (mth) 1-year1,5-year3-year5-year Zhou X.D., 1992 (n= 30, d<5 cm) 60.532.020.219.2 Crew K.A., 1997 (n=8)60.217.7 Zhou X.D., 1998 (n= 235)78.454.139.838.2 Rehrig S.T., 2001 (n=8)41.824.0 Xu K.C., 2007 (n=14, d>5 cm) 71.450.021.418.0 Results of cryoablation for HCC

5. Survival (%)Median survival (mth) 1-year3-year5-year Korpan N.N., 1997 (n=8)604442 Ruers T.J.M., 2001 (n=30)76583832 Wallace J.R., 2001 (n=137)86472923 Goering J.D., 2002 (n=42)82553945 Kerkar S., 2004 (n=98)81482833 Jungraithmayr W.,2005 ( n=17) 5210521 Results of cryoablation for colorectal liver metastases

6. Survival (%)Median survival (mth) 1-year1,5-year3-year5-year Kovach S.J., 2002 (n=9)40224-5 Xu K.C., 2002 (n=59)34.5242-8.4 Results of cryoablation for pancreatic cancer

7. Aim: to improve the quality of life in patients with primary and metastatic liver and pancreatic cancer.

8. Since 2007 cryolysis was performed in 82 patients (36cases – for HCC and liver metastases and 46 for pancreatic cancer).

9.  Cancer of head –32, corpus – 14.  Mean age was 42+2 years.  Size of lesions in the pancreas ranged from 2.5 to 6 cm in length.  Cancer: IV st. – 36 pts., III st. – 10. Cancer of the pancreas (n=46) (n=46)

10.  Mean age was 49+2 years.  Size of lesions in the liver ranged from 1.5 to 10 cm in length.  Number of lesions in the liver - from 1 to 10 (4±3).  Mts (n=17): IV st. – 19, III st. – 5. Liver malignancy (n=36) (n=36) F n = 16 M n = 8 HCC (n = 12) Mts (n = 24) M n =8

11. Cryoprobes Cryoprobes Time of cryolysis ranged from2 to 5 minutes at t° - from 175°C - to 186°C. Number of sessions at one lesion was from 1 to 5.

12. US and CT cancer of the pancreas

13. Сancer of the pancreas Intraoperative view: pre – (a) and postcryoablation (b ) a b

14. Intraoperative US The pancreatic ultrasound imaging before (a), intra- (b) and after cryoablation (c) a bc

15. Moderately differentiated adenocarcinoma metastasis (neoplastic glands are chaotically embedded in fibrous stroma with extravasation) Neoplastic structures are partially destroyed at the center. Per high power field destruction of tumor cells cytoplasm is observed, no cell boundaries. Hyperchromic nuclei, no endonuclear structures. (As at coagulation necrosis)

16. MRI Colorectal liver metastases

17. LIVER METASTASES Intraoperative view: before – (a), during- (b) and after cryoablation (c) a a bc

18. Immunohistochemical test with Ki67 shows no nuclear reaction in the majority of tumor cells. Immunohistochemical test with Ki67 shows some nuclear reaction in occasional cells peripherally. Cells in smaller neoplastic glands preserve the ability of segmentation (Immunohistochemical test with Ki67, brown staining in nuclei).

19. Intraoperative ultrasound The liver ultrasound imaging during- (a) and after ablation (b) а b

20. Case report

22. Cryoablation was performed before biliary bypass procedure in 84% and gastroenterostomy in 32%. In 3 patients with HCC and one with MTS colorectal cancer cryoablation was combined with postoperative percutaneous alcoholization of the lesions. TACE was performed in 9 cases. Adjuvant chemotherapy was performed in all patients.

23. Short-term results : major complications 2 (3,4%): -intra-abdominal hemorrhage minor complications 4 (6,9%): - acute pancreatitis (n = 2), - wound abscesses (n = 2). Postoperative mortality - 0 72% of patients with pancreatic cancer had effective pain control

24. Long-term results: The maximum follow-up period was 30 months. Of the 5 patients with tumor spread beyond the liver one female is currently alive with a follow-up period of 30 months. Currently, there are no patients alive with tumor spread beyond the pancreas. Totally, there are two patients who survived 30 months. Pancreatic cancer (n = 46): IV stage - 36 patients, III - 10. MTS in the liver (n = 24): IV stage - 19 patients, III stage- 5. HCC (n = 12): Currently 2 patients are alive.

25. Cryoablation for liver metastases Survival analysis - 6 months. - 88%, - 12 months. - 76%, - 24 months. - 50%, - 33 months. - 25%.

26. Cryoablation for НСС Survival analysis

27. Cryoablation for pancreatic cancer Survival analysis

28. Conclusion: Cryoablation for HCC, liver metastases and advanced pancreatic cancer is promissing method in term of improving the quality of life as well as long term survival. Neoadjuvant and adjuvant chemotherapy may improve the long term results of cryoablation. Research in the field of cryobiology should be continue for optimization of the protocol of cryoablation for malignant tumors.

29. THANK YOU !