1. 3rd Annual Conference on Gynecologic Oncology & Preventive Oncology July 20-21, 2017 Chicago, Illinois, USA Theme: Revolutionary Essence of Motivating the Living and Good Health of Women
Nanoknife Irreversible Electroporation (IRE) for the Treatment of Pancreatic and Liver Tumors
Aaron H. Chevinsky, MD FACS
Director of Surgical Oncology
Aurora Health Care
Milwaukee, WI
Adjunct Clinical Assistant Professor of Surgery
University of Wisconsin-Madison
School of medicine and Public Health

3. Hepatobiliary and Pancreatic Cancer Multi-Disciplinary Team Goals
Improve Patient Care and Expand Access
Coordination of New Technology
Multidisciplinary tumor evaluation teams and conferences
Enhanced Patient and Physician Education
Brochures
Symposia
Outreach
Increasing Clinical Trial Enrollment
Prioritize Protocols
Pancreas and Liver Tumor Database
Boost Public Awareness
Public Relations and Marketing

4. GI/HB/Pancreatic MDC - Team Integration
Medical Specialties
Hospital Services
Operating Room
Inpatient Oncology
Outpatient Oncology
Nursing
Intensive Care Unit
Research
Oncology Dieticians
Social Work
MBI /Complementary Medicine
Medical Oncology
Radiation Oncology
Surgical Oncology
General Surgery
Colorectal Surgery
Gastroenterology
Radiology/IR
Pathology
Psychiatry
Palliative Care

5. Multi-Disciplinary Planning
Goal is for patients to be evaluated expeditiously by surgical, medical and radiation oncology after presentation at Multi Disciplinary Committee (MDC)
Nurse Navigator to meet with patient and family to help arrange visits and tests and follow after surgery/treatment
Nurse Navigator to assist with patient education and coordination of services
Review of pathology and radiology
Case conference discussion
Opinion rendered to patient
Treatment started

6. Hepatobiliary and Pancreatic Cancer Demographics
53,670 Cases in the US in 2017 (2% of all cancers)
43,090 Deaths in the US in 2017 (6% of deaths)
Primary Liver and Intrahepatic Biliary Cancers
40,710 Cases in the US in 2017
28,920 Deaths in the US in 2017
GB and Biliary Tree
11,740 Cases in the US in 2017
3,830 Death in the US in 2017
Liver Metastases – Colorectal, Neuroendocrine…
135,430 CRC – 30-40,000 with isolated liver metastases

7. What is The NanoKnife Procedure?
The NanoKnife* System is intended for the surgical ablation of soft tissue.
An ablation procedure that uses low energy electrical pulses to create defects (pores) in cell membranes, resulting in loss of homeostasis and subsequent cell death 1.
Uses high voltage, but low energy direct current (LEDC)
does not rely on heat to ablate tissue.
The process with which LEDC ablates soft tissue is known as electroporation or irreversible electroporation (IRE) 1.
Lee EW; “Advanced hepatic ablation technique for creating complete cell death: irreversible electroporation”; Radiology May

8. Pancreatic Cancer Definitions: Based on CT Scanning
The Pancreas
Pancreatic Cancer Definitions: Based on CT Scanning
Resectable
No extension to celiac, CHA, SMA, patent SMV/PV confluence
Stage I, II (T13, Nx, M0)
Locally advanced
Celiac, SMA encasement (>180), occlusion of SMV/PV confluence
Stage III (T4, Nx, M0)
Borderline
Severe SMV/PV impingement, SMA abutment, GDA encasement up to HA, colon or mesentery involvement
Stage III (minimal T4)
AHPBA/SSO Consensus Conference, 2008
Ann Surg Oncol 13(8) Ann Surg Oncol 16:

9. Resectable Will need PV resection SMV SMV SMA SMA
The Pancreas
Resectable
Will need PV resection
SMV
SMV
SMA
SMA T
Not currently resectable
Borderline resectability
SMV
SMV
SMA
SMA
Kitts
Resectable tumor, RRHA

10. Location is Everything

11. RF lesion deflected by large blood vessels (see arrows)
Liver RFA Limitations
Local recurrence rates: 20%-30%
Limited RFA lesion dimensions necessitate multiple applications
Higher recurrence rates for large tumors
Large vessels
Large vessels act as heat sinks
Higher recurrence rates for tumors near large vessels
Biliary strictures
RFA adjacent to major bile ducts may result in stricture formation
RF lesion deflected by large blood vessels (see arrows)

12. Nanoknife Irreversible Electroporation
NanoKnife System consists of the generator (pictured at right), footswitch, power cord, and a line of single-use disposable electrodes. System has:
Up to 6 outputs with programmable, automatic switching between each output.
USB port to download patient data.
System has received FDA clearance for the surgical ablation of soft tissue.  It has not received clearance for the therapy or treatment of any specific disease or condition

13. NanoKnife System Monopolar Electrode Key Features Single Electrode
Disposable
15 cm length
25 cm length
Key Features
19 gauge needle with depth markings
Echogenic needle surface
Active electrode length adjustable in 0.5 cm increments from 0 – 4 cm
8 foot connection cable

14. How The Technology Works
Rapid series of short, electrical pulses
Low energy direct current (LEDC)
High voltage, but low energy
Does not rely on heat to ablate tissue
Defects (“pores”) created in cell membrane
Cell death occurs in the ablation zone
Notes: The amount of reversible electroporation achievable (360 V cm−1 threshold, outer contour line) as compared to the amount of irreversible electroporation achievable (680 V cm−1 threshold, inner contour line) with the electric field (V cm−1) superimposed due to an 800-μs, 1331-V pulse for a two-electrode configuration, 1-mm diameter and 10-mm
center-to-center spacing. (Davalos et al, Tissue Ablation with Irreversible Electroporation; Annals of BioMed, Feb 2005)
Notes: The amount of reversible electroporation achievable (360 V cm−1 threshold, outer contour line) as compared to the amount of irreversible electroporation achievable (680 V cm−1 threshold, inner contour line) with the electric field (V cm−1) superimposed due to an 800-μs, 1331-V pulse for a two-electrode configuration, 1-mm diameter and 10-mm
center-to-center spacing. (Davalos et al, Tissue Ablation with Irreversible Electroporation; Annals of BioMed, Feb 2005)

15. NanoKnife® System Overview
Uses high voltage, low energy electrical pulses to achieve tissue effect
Does not rely on heat to ablate tissue
Poses no heat sink issues
Well demarcated post ablation zone
Allows real-time CT/US imaging of ablated zones

16. Visualized Under Ultrasound
Example showing hypo-echoic ablation zone immediately after ablation.
Ablated area correlates to the hypoechoic image immediately
post-ablation and to gross pathology.
Immediately Post-Ablation
“Irreversible Electroporation; A New Ablation Modality-Clinical Implications; Technology in Cancer Research and Treatment, ISSN Vol. 6 Number 1 Feb. 2007

17. ECG Synchronization External synchronization device.
The ECG Trigger Monitor automatically detects the R Wave (when energy is delivered) with precision and reliability per its manufacturer.
Synchronization device senses the rising slope of the R-wave, and sends a signal to the NanoKnife® System, which waits 50 milliseconds (.05 sec) and delivers 1 energy pulse. The energy pulse is delivered during (or just before) the ventricular refractory period.
Refractory
Period
Vulnerable

18. Nanoknife Procedure
Ablation with the NanoKnife System requires general anesthesia and muscle blockade
Procedure requires muscle blockade during energy delivery
0/4 to 1/4 twitches on the Train of Four Test
High energy pulses could interfere with ECG monitor- an alternative monitor such as a fast pulse oximeter or arterial line should be available
Patient positioned to best facilitate access to the ablation area
Synchronization recommended is 5 ECG buttons with electrodes placed in standard position

19. Nanoknife

20. Nanoknife – Literature Review
Study
Open or IR
Total Tx #/Pts
# Panc
# Liver
Mean Tumor
Size
Comp
Mortality
Narayanan
2012 IR
13/12 13
3 cm
2 -Pancreatitis, Pneumothorax (15.4%)
Martin
Open 27
17 - (63%) PV Thrombosis-2, Bile Leak -2, Ascites-1
1:17 (6%)
Martin 2012 54
3.2 cm
25 – (46%) PV Thrombosis, Bile Leak, Duodenal Leak
1:54 (1%)
Kingham
22 open 6 IR
65 Txs 28 PTS 28
1 cm
3% - 1 PV thrombosis
Cannon
2013
48 Txs
44 Pts 44
2.5 cm
10%
J Vasc Interv Radiol 2012; 23:1613–162, J Am Coll Surg363 Vol. 215, No. 3, September 2012 , Ann Surg Oncol (2013) 20:S443–S449, J Am Coll Surg Vol. 215, No. 3, September 2012 , Journal of Surgical Oncology 2013;107:544–549

21. IRE was successfully performed in all patients
Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients With Irreversible Electroporation: Safety and Efficacy
200 pts with locally advanced pancreatic cancer had IRE (n = 150) or resection plus IRE for margin enhancement (n = 50)
All pts had induction chemotherapy/52% received chemoradiation therapy for a median of 6 months before IRE
IRE was successfully performed in all patients
Median 4 probes (2 for margin accentuation)
Complication rate was 37%
Median LOS was 6 days
Local Recurrence rate was 3% after a median F/U of 29 months
Median overall survival was 24.9 months (range: 4.9–85 months).
Median survival of locally advanced pancreatic cancer is mos
Martin et al. Annals of Surgery: September :

22. Nanoknife Case GR
73 year old female admitted with painless obstructive jaundice
CT scan and EUS demonstrate involvement of portal confluence
Biliary stent placed
Treated with chemotherapy (GAX)
Gemcitabine/Abraxane/Xeloda
Follow-up CT with decrease in tumor still with involvement of portal confluence

24. Tumor
SMV
Post Chemotherapy

26. Pancreatic
Tumor

27. Tumor Around
SMV/PV

28. Probe
Placement

29. Nanoknife Case DC
71 year old male diagnosed with an unresectable pancreatic malignancy in 7/2013
Tumor encasing SMA/SMV
Started on chemotherapy with FOLFIRINOX
Received 5 weeks of RT
Tumor persisted on CT Scan
SMV occluded with Varices

30. Varices
Pancreatic Mass

33. Nanoknife – Case AC 55 year old male diagnosed with rectal cancer
Treated with neoadjuvant chemotherapy and RT followed by Low anterior resection
Found to have liver metastases
Treated with chemotherapy which was poorly tolerated
Had 5 liver metastases
3 resected, 2 treated with Nanoknife

35. Tumor
IVC/RHV

36. Liver Mass
Hepatic Vein/IVC
Probes

38. Nanoknife – Technical Considerations
CT or MRI should be done within 1 month of procedure
Follow-up Scan in 6 weeks - 3 months
Can be used as an adjunct to resection or as a stand alone Maximum treatable tumor size is CM
Most cases will require 3-4 probes placed under ultrasound
Laparoscopy should be done to evaluate for metastases
Irrigate with Sterile Water not Saline (Non-Conductive)
Metal Stents must be removed prior to or at surgery
Biliary/gastric bypass may be necessary as a concomitant procedure
Both open and IR techniques Available
SMV Occlusion and Varices not a contraindication
Pts with Pacemakers, AICD or in rapid Atrial Fibrillation cannot be done