Investigating Signal Change in Malignant and Non-malignant Pleural Effusions and asCitic Fluid Using fTiR Analysis

Overview

Lung cancer is a common cancer, associated with a high mortality rate. Pleural effusions are common in lung cancer, developing in up to 40% of patients. Ascites is common in patients with abdominal malignancies and can be the presenting feature in up to 50% of patients. There is a need for new techniques to improve our diagnostic ability of cancer. FTIR technology could enable a point-of-care test that would provide an initial diagnosis that may determine a change in treatment at the time of the investigation.

Lung cancer accounts for 13% of all new cancer cases in the UK and is the third most common cancer. However, lung cancer has the highest mortality rate, thought partly related to late diagnosis. Pleural effusions develop in up to 40% of patients with lung cancer, and can be the first presenting sign. Current methods of analysing pleural fluid are based on using Light's criteria to distinguish between exudates and transudates depending on the protein and LDH component of the fluid. However, this system does not discriminate between causes of exudative effusions for example malignant effusions vs infective causes. Pleural fluid cytology can identify malignant effusions but gives an average yield of 60% through a labour intensive and time consuming process. If pleural fluid cytology is non-diagnostic, patients require further invasive investigations such as local anaesthetic thoracoscopy, lymph node biopsies or image-guided biopsies to gain a tissue diagnosis. Therefore, determining an alternative, accurate method of diagnosing cancer at the earliest opportunity would reduce the need for further invasive investigations and would provide patients with increased treatment options, thereby increasing survival rates. There are differences in the biochemical composition of malignant and non-malignant effusions thereby offering an opportunity to develop alternative techniques of investigating the cause of these effusions. Ascites is a common symptom of patients with various underlying cancers; most commonly breast cancer, colon cancer, gastrointestinal cancer and ovarian cancer, and is often associated with significant morbidity. However, up to 50% of patients with malignant ascites present with ascites as the first feature. This symptom is not specific to any type of cancer; current investigations including using serum tumour markers have a low diagnostic specificity and there is a need for new techniques to improve our diagnostic ability. Fourier transform mid-infrared spectroscopy (FTIR) is a reproducible and relatively simple investigation used to analyse the structural components of tissue or cells. As infrared light is passed through a sample, some light is absorbed and some transmitted through. The resulting signal at the detector presents as a spectrum, representing a 'molecular fingerprint' of the sample. Each chemical structure produces a unique spectral fingerprint making FTIR a useful tool for identifying components of tissue or cells. Attenuated Total Reflection Linear Variable Filter (ATR-LVF) spectroscopy is a variant of IR spectroscopy in which samples can be examined directly with no preparation needed. ATR-LVF spectroscopy can be performed on benchtop spectrometers with minimal operator training and an immediate result can be obtained. Both FTIR and ATR-LVF are non-invasive, reproducible, do not damage the sample and have the benefit of only requiring a small sample size to generate results all of which are desirable qualities in developing a new investigation. FTIR has been used to successfully discriminate between malignant and non-malignant lung tissue6, and also to identify spectral differences in samples of pleural fluid from malignant and non-malignant participants. There is currently ongoing work investigating FTIR in diagnosing malignant pleural mesothelioma and initial results have shown significant spectral differences in this population too. There is very little information regarding the use of FTIR in assessing ascitic fluid. However, despite the technology, it is not available as a bedside point-of-care test for clinicians. The differences and discrimination of the model has not been tested prospectively to determine sensitivity and specificity of the FTIR test. A mobile point-of-care devices that may be able to provide rapid diagnostic results. This study aims to confirm that the spectral changes between malignant and non-malignant samples are present in a UK population in both pleural effusions and ascites.