Use of iKnife instrument during standard operative practice

Rapid Evaporative Ionisation Mass Spectrometry (REIMS)

Adele Savage

James Kinross

Zoltan Takats

There are currently no widely accepted methods which provide real time in vivo, in situ tissue diagnostics within the operating theatre environment.

This project proposes that the oncological nature of in vivo tissue may be accurately identified using mass spectrometric analysis of tissue specific ions released during thermal degradation of tissue as occurs during electrosurgery.

Subsequently, the protocol describes a technique for a prospective study to determine whether Rapid Evaporative Ionisation Mass Spectrometry (REIMS) can be used to accurately identify the nature of human tissue both ex vivo and in vivo.

The project aims/objectives comprise the following:

1. Building of histologically validated spectral databases for normal, benign and malignant tissue using ex vivo tissue analysis by Rapid Evaporative Ionisation Mass Spectrometry (REIMS).
2. Optimisation of a technique to provide accurate, real-time information on the nature of tissue intra-operatively using Rapid Evaporative Ionisation Mass Spectrometry.
3. Optimisation of a technique to provide accurate, real-time information on the nature of tissue during endoscopic procedures using Rapid Evaporative Ionisation Mass Spectrometry.
4. In vivo testing of the accuracy of the technique using pre-built spectral databases both intraoperatively and during endoscopic procedures including, but not limited to, the use of sub-study trials.
5. Validation of spectral data obtained using a second mass spectral analysis technique, Desorption Electrospray Ionisation Mass Spectrometry (DESI).
6. Bacterial identification from tissue using mass spectrometry, standard microbiology culture and metagenomic sequencing by '454 pyrosequencing.

The following will be collected from each enrolled participant:

1. Fresh ex vivo tissue samples for mass spectral (MS) analysis and histological examination where applicable
2. In vivo MS data from surgical diathermy smoke collected intra-operatively.

Custom built Mass spectrometers will be installed at participating sites. Optimal electrosurgical settings, in terms of obtaining maximal amount of good quality spectral data whilst providing adequate surgical dissection, will be determined between operating surgeons and researchers.

All spectral data collected will be uploaded anonymised into a research database with the full histology provided. The spectra will be pre-processed according to the mass spectrometer used for collection.

In addition to diagnostic accuracy REIMS offers additional advantages to existing and emerging IMA techniques. Specifically, the REIMS iKnife allows use of a standard operating procedure without altering operative workflow in that the technique samples the surgical aerosol already being generated during excision. The rapid time frame of analysis to results (1-2 seconds) means that eventually surgeons' decision-making may be altered in real-time to achieve negative margins or improve patient prognosis.

Fresh ex vivo tissue samples for mass spectral (MS) analysis and histological examination where applicable (may be retained for long term storage and may be used in subsequent research including genetic testing, subject to having ethical approval)

iKnife REIMS Project

Real Time Tissue Characterisation Using Mass Spectrometry

To determine whether Rapid Evaporative Ionisation Mass Spectrometry (REIMS) can be used to accurately discern between cancerous and normal tissue both in vivo and ex vivo

The primary end-point is accuracy (sensitivity and specify) of rapid ionisation mass spectroscopy to distinguish between patients with at least one close or positive margin and those without close or positive margin.

Imperial College London

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Endometrial Neoplasms

Hyperplasia

Endometrial Hyperplasia

Uterine Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Single study arm. All patients who participate in the study will receive conventional histological diagnosis and diagnosis with the new technology (iKnife)

The endometrial tissue will be analysed by this new technology and compared to gold standard (histopathology)

iKnife i.e. Rapid Evaporative Ionisation Mass Spectrometry

Aim: Determine if Rapid Evaporative Ionization Mass Spectrometry (the iKnife); can diagnose cancer and pre-cancer from endometrial tissue biopsy samples.

Women attending a gynaecology clinic for assessment of abnormal bleeding will receive an pelvic (internal) ultrasound as routine standard of care. If any abnormalities are detected, a tissue sample will be needed. If women are agreeable a second tissue sample will be taken for research. The first will be analysed by conventional means (histopathology). The second sample with new technology called the 'iKnife'. This is a modified type of Mass spectrometry device, that separates particles based on their mass charge ratio. The idea being that if tissue is burnt, gas is produced, and this gas contains lots of ions that can be analysed by the iKnife. Each type of tissue (cancer or non-cancer) will have a unique signature that the iKnife can use to distinguish between samples. If effective it could be used in future outpatient clinics to provide a one-stop, true point of care diagnosis.

Aim: Determine if Rapid Evaporative Ionization Mass Spectrometry (the iKnife); can diagnose cancer and pre-cancer from endometrial tissue biopsy samples.

Background:

Endometrial cancer is a tumour originating in the endometrium (womb lining); it is the most common gynaecological cancer in the United Kingdom (UK). In 2012, there were almost 100,000 new cases diagnosed in Europe. Endometrial cancer classically presents with postmenopausal bleeding (bleeding after the menopause), or intermenstrual bleeding (bleeding between periods).

Although routine management for these women does vary, in general a screening test is performed, typically a pelvic (internal) ultrasound to assess the endometrium (womb lining). In cases where the endometrial thickness is above the threshold for investigation -an endometrial biopsy (sampling cells from the womb lining) is indicated.

Once the endometrial biopsy is performed, it is sent to the histologist for further examination. Histological analysis may take several days and patients are either brought back to clinic for discussion of the results or are given a telephone appointment. The patient often will not know the result of the test for up to 2 weeks; thus causing a lot of unnecessary anxiety and distress. Novel diagnostic tests, such as Rapid Evaporative Ionization Mass Spectrometry (REIMS), may enable real time point of care diagnosis for the first time. When REIMS is coupled to conventional surgical diathermy it is colloquially referred to as the iKnife. REIMS has been used successfully in other organs and has been shown to accurately distinguish between cancer and non-cancer. Part of this research project is to evaluate this new technology in endometrial cancer.

The study:

All women presenting to the rapid access clinic with post menopausal bleeding (PMB) and intermenstrual bleeding will be approached for consent for inclusion into this study. They will receive the patient information leaflet when they arrive in clinic and are waiting to see the clinician. When women normally attend this clinic the doctor will discuss what will happen - this includes an internal (pelvic scan) and an examination. If the womb lining is thickened on the scan the patient will need a tissue biopsy (this is not that common, most women only need a scan), this will be taken at the same time as the examination in clinic. The device used to take the tissue biopsy is called a pipelle. It is a fine 3mm width tube with suction which removes cells from the lining of the womb. If the patient is agreeable a second endometrial sample will be taken specifically for research.

The histology of first sample will be analysed by conventional pathology and the second sample will be analysed by the new technology REIMS. REIMS is Rapid Evaporative Ionization Mass Spectrometry. This new technology uses mass spectroscopy to analyse the tissue. REIMS has been dubbed the 'iKnife' or 'intelligent knife' colloquially as when coupled with surgical diathermy the gas pattern produced is unique to the tissue and helps surgeons know where to cut. The diagnostic ability of this technology will be compared against the gold standard, which is histological examination.

Patients who already have a diagnosis of endometrial cancer and can still participate in the study if they are undergoing a hysterectomy, as can consent to an tissue biopsy sample in theatre (either under general anaesthesia, GA or ex-vivo).

If this technology proves effective it will mean that womb (endometrial) cancer can be diagnosed from samples taken in clinic on the same day; providing a true one stop clinic, for the first time.

Study is looking at endometrial cancer so recruitment of women only

Can the iKnife Distinguish Between Normal and Malignant Endometrial Tissue?

Pilot Study: Can the iKnife (Rapid Evaporative Ionisation Mass Spectrometry) Distinguish Between Normal and Malignant Endometrial Tissue?

Sensitivity, specificity and positive and negative predictive values will be obtained for this new technology compared to gold standard (histopathological exam).

Test sensitivity is the ability of the iknife to correctly identify those with endometrial cancer (true positive rate).

Test specificity is the ability of the iKnife to correctly identify those without endometrial cancer (true negative rate).

Positive predictive value is the probability that patients with a positive iKnife test result truly have the disease.

Negative predictive value is the probability that patients with a negative screening iKnife test truly don't have endometrial cancer.

The patients provided a tissue biopsy sample for research (in addition to the tissue sample provided for clinical indications).

No extra additional risk for the patient. However, tissue biopsy can be inadequate, or can cause perforation (1-2%). There is negligable additional risk with the extra research tissue needed.

Single study arm. All patients who participate in the study will receive conventional histological diagnosis and diagnosis with the new technology (iKnife).

All Patients

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United Kingdom

Region of Enrollment

Body Mass Index (BMI)

Dr Diana Marcus

Sensitivity

Specificity

Positive Predictive value

Negative predictive value

Analysis of diagnostic accuracy of iKnife from endometrial pipelle biopsies

Diagnostic Ability of iKnife (REIMS) in Detection of Cancer and Pre-cancer in Endometrial Biopsy Specimens

Single study arm. All patients who participate in the study will receive a tissue biopsy, one processed with the conventional histology and one processed with the iKnife (Rapid Evaporative Ionisation Mass Spectrometry).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
iKnife REIMS Project	NCT04067388	Neoplasms Neoplasm Malign...	Rapid Evaporati...	18 Years -	Imperial College London
Can the iKnife Distinguish Between Normal and Malignant Endometrial Tissue?	NCT03207074	Endometrial Neo... Endometrial Can... Endometrial Hyp... Endometrial Dis...	iKnife i.e. Rap...	18 Years -	Imperial College London

Spots Global Cancer Trial Database for iknife

Every month we try and update this database with for iknife cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for iknife

Every month we try and update this database with for iknife cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for iknife cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.