Potential game changer in
surgeryJames Kong
Yan Chai Hospital
Definition
• Game changer : – a newly introduced element or factor that changes an existing
situation or activity in a significant way
Source: Merriam-Webster dictionary
Cancer Operation
• Existing situation:– Diathermy for dissection– Frozen section for margin identification
Current practice
• Electrocautery produces “surgical smoke” as a by-product
• Smoke – mutagenic and therefore genotoxic– irritant
• Get rid of them– suction– evacuation systems
Surg Endosc. 2003 Jun;17(6):979-87
Current practice
• Clear margin– Depends on surgeons visual and tactile feedback– Intraoperative frozen section
• Time consuming– Increased GA time– Prolongs operation
• Costly• Limited number of sampling points• Pathologist dependant esp. in suboptimally prepared or non-
oriented specimen
• New idea?
New technology• iKnife• Diathermy + Rapid evaporative ionization mass
spectrometry (REIMS)• Standard electrosurgical knife connected to a mass
spectrometer which identifies chemicals in a compound based on the mass of the molecules
• Smoke produced by healthy vaporized tissue differs in chemical composition from cancerous tissue
Latest Evidence
Sci Transl Med 17 July 2013: Vol. 5, Issue 194, p. 194ra93
Methods• Collected data ex vivo from benign and malignant gastric, colonic,
hepatic, breast, lung, and brain tissue samples from 302 patients• Created a histologically specific mass spectral reference library• 2933 histologically validated database entries• Identified compounds included phosphatidylethanolamines,
phosphatidylcholines, phosphatidic acids, phosphatidylserines, phosphatidylinositols, sphingomyelins, cardiolipins, plasmalogens, and sulfatides
Results• Most of the lipid species were detected across multiple
tissue types• Distribution patterns were markedly distinct for healthy
versus cancerous tissues profile of species accounts for histological specificity
Healthy tissue• Reproducibility of REIMS data sufficiently good for
unambiguous identification of major tissue types
Solid tumors• Complete separation of different histologically specific
data points strongly suggests that mass spectrometric identification of different lung tumors is feasible
Solid tumors • Data points corresponding to bulk tumor tissue separate
well from the surrounding healthy liver tissue, and data points collected every 1 cm from the visible tumor indicate a gradual metabolic transition from a benign to a malignant tissue phenotype (arrow)
Metastases• Astrocytomas with different WHO grades can by clearly
differentiated from brain metastases• Brain metastases from different primaries show specific
lipidomic phenotypes as confirmed by histopathology (colon and lung)
Metastases• Field transition not observed for
metastases• Analysed liver metastases from
colon• Parallel sampling lines 1 to 2 mm
apart were taken using a continuous burn, which started in the healthy region and continued through the center of the cancer
• Correctly identified 73 sampling points, with two false-negative and one false-positive
`Metastasis from colonAdenocarcinoma in liver
Healthy liver parenchyma
Metastasis from colonAdenocarcinoma in liver
Healthy liver parenchyma
Results
• Database used for intraoperative testing• 864 spectra were acquired from 81 patients• Distinguishing cancer vs. healthy tissue
– Sensitivity 97.7%– Specificity 96.5%
• Subclass analysis: – Primary liver and malignant lung tumors– Specificity 92-94% only
Potential• ~20% breast cancer patients with lumpectomy require further surgery to clear
positive margins1
• Potential to influence “on-table” decision-making and lower reoperation rates• Entire procedure including sampling, sample transfer, chemical analysis, data
processing, and audiovisual feedback takes ~0.7 to 2.5 s, compared to ~30 min for intraoperative histopathology
• Could improve cosmetic and functional outcomes by minimizing unnecessary removal of healthy tissue
• More sampling points than frozen section• Potentially shorten surgical procedure• Potential to reduce local tumor recurrence rate and the cost of histopathology
services and improve overall patient survival
1R. Jeevan et al. Reoperation rates after breast conserving surgery for breast cancer among women in England: Retrospective study of hospital episode statistics. BMJ 345, e4505 (2012).
Far from perfect• Observational study, 3 hospitals in Hungary• Requires a histologically specific mass spectral library of a
good quality– Only determined in retrospective way– Initial stage impossible to identify every tissue type eg. rare tumors
• Cost and effort of developing device and spectral database• Surgeons blinded to test results intraoperatively• No solid evidence of advantage with intraoperative use• No evidence of survival benefit• No evidence it reduces local recurrence rate
Observational study Limited database Cost No study on influence over
intraoperative decision making No RCT to justify its advantage (if
any) over current practice No proven survival benefit
Observational study Limited database Cost No study on influence over
intraoperative decision making No RCT to justify its advantage (if
any) over current practice No proven survival benefit
Speed Unlimited sampling points Shorten operative time Preserve more healthy tissue Identify exact tissue type Reduce cost of frozen section
Speed Unlimited sampling points Shorten operative time Preserve more healthy tissue Identify exact tissue type Reduce cost of frozen section
Summary
NegativeNegativePositivePositive NegativeNegativePositivePositive
Conclusion
• Can it replace intraoperative frozen section?• Initial results look promising (as with all new
technological innovations)• iKnife technology is still in its early stage• RCTs are mandatory to justify its use• Until it demonstrates a clear benefit to
patients and the health care system it would not be widely available
The End
Mass spectrometry• Stage 1: ionization• Stage 2: acceleration• Stage 3: deflection (by magnetic field)• Stage 4: detection
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