Breast cancer is a heterogeneous disease characterized by varying responses to therapeutic agents and significant differences in long-term survival. Thus, there remains an unmet need for early ...diagnostic and prognostic tools and improved histologic characterization for more accurate disease stratification and personalized therapeutic intervention. This study evaluated a comprehensive metabolic phenotyping method in breast cancer tissue that uses desorption electrospray ionization mass spectrometry imaging (DESI MSI), both as a novel diagnostic tool and as a method to further characterize metabolic changes in breast cancer tissue and the tumor microenvironment. In this prospective single-center study, 126 intraoperative tissue biopsies from tumor and tumor bed from 50 patients undergoing surgical resections were subject to DESI MSI. Global DESI MSI models were able to distinguish adipose, stromal, and glandular tissue based on their metabolomic fingerprint. Tumor tissue and tumor-associated stroma showed evident changes in their fatty acid and phospholipid composition compared with normal glandular and stromal tissue. Diagnosis of breast cancer was achieved with an accuracy of 98.2% based on DESI MSI data (PPV 0.96, NVP 1, specificity 0.96, sensitivity 1). In the tumor group, correlation between metabolomic profile and tumor grade/hormone receptor status was found. Overall classification accuracy was 87.7% (PPV 0.92, NPV 0.9, specificity 0.9, sensitivity 0.92). These results demonstrate that DESI MSI may be a valuable tool in the improved diagnosis of breast cancer in the future. The identified tumor-associated metabolic changes support theories of de novo lipogenesis in tumor tissue and the role of stroma tissue in tumor growth and development and overall disease prognosis.
Gastrointestinal cancers are a leading cause of mortality, accounting for 23 % of cancer‐related deaths worldwide. In order to improve outcomes from these cancers, novel tissue characterization ...methods are needed to facilitate accurate diagnosis. Rapid evaporative ionization mass spectrometry (REIMS) is a technique developed for the in vivo classification of human tissue through mass spectrometric analysis of aerosols released during electrosurgical dissection. This ionization technique was further developed by utilizing surface induced dissociation and was integrated with an endoscopic polypectomy snare to allow in vivo analysis of the gastrointestinal tract. We tested the classification performance of this novel endoscopic REIMS method in vivo. It was shown to be capable of differentiating between healthy layers of the intestinal wall, cancer, and adenomatous polyps based on the REIMS fingerprint of each tissue type in vivo.
Inside story: Rapid evaporative ionization mass spectrometry (REIMS) was integrated with an endoscopic polypectomy snare to enable in vivo analysis of the gastrointestinal tract. This novel endoscopy method was shown to be capable of differentiating between healthy layers of the intestinal wall, cancer, and adenomatous polyps based on the REIMS fingerprint of each tissue type in vivo.
The morphological transformation of beef tissues after various processing treatments facilitates the addition of cheap offal products. Undetectable to the naked eye, analytical techniques are ...required to identify such scenarios within minced and processed products. DNA methodologies are ill-equipped to detect adulteration of offal cuts from the same species and vibrational spectroscopic studies, although rapid and non-destructive, have proved inconclusive as to whether the specific adulterant can be identified. For the first time we present a mass spectrometric approach employing an ambient ionisation process to eliminate sample preparation and provide near-instantaneous results. Rapid evaporative ionisation mass spectrometry (REIMS) was used to assess its capabilities of detecting minced beef adulteration with beef brain, heart, kidney, large intestine and liver tissues and chemometric analysis enabled unique or significant markers to be identified. The adulteration levels detected with the REIMS technology when analysing raw adulterated beef burgers were; brain (5%); heart (1-10%); kidney (1-5%); large intestine (1-10%) and liver (5-10%). For boiled adulterated samples; brain (5-10%); heart (1-10%); kidney (1-5%); large intestine (1-10%) and liver (5-10%). REIMS allows rapid and specific identification of offal cuts within adulterated beef burgers and could provide a paradigm shift across many authenticity applications.
Background
This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas.
Methods
Patients undergoing ...elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy.
Results
Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy.
Conclusion
REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer.
Next‐generation imaging mass spectrometry of biological tissue on the cellular level shows excellent agreement with histochemical evaluation whilst providing a much higher discrimination capacity ...based on label‐free molecular information (see image of a mouse urinary bladder section).
Background
Transanal minimally invasive surgery (TAMIS) is deployed for organ preservation in early rectal cancer and significant rectal polyps. Rapid evaporative ionisation mass spectrometry (REIMS) ...provides biochemical tissue analysis, which could be applied intraoperatively to give real-time tissue feedback to the surgeon and decrease the risk of an involved margin. However, the accuracy and feasibility of this approach have not been established.
Methods
In this prospective observational study, patients undergoing resection of rectal adenomas or carcinomas were recruited. An electrosurgical handpiece analysed tissues ex vivo using diathermy, with the aerosol aspirated into a Xevo G2-S ToF mass spectrometer. The relative abundance of lipids underwent predictive statistical modelling and leave-one-patient-out cross-validation. The outcomes of interest were the ability of REIMS to differentiate normal, adenomatous and cancerous tissue, or any disease subtype from normal. REIMS was coupled with TAMIS for in vivo sampling, assessing the accuracy of tissue recognition and distinguishing bowel wall layers.
Results
Forty-seven patients were included, yielding 266 spectra (121 normal, 109 tumour and 36 adenoma). REIMS differentiates normal, adenomatous and cancerous rectal tissues with 86.8% accuracy, and normal and adenomatous tissue with 92.4% accuracy and 91.4% accuracy when differentiating disease from normal. We have performed the first five in-man mass spectrometry augmented TAMIS (MS-TAMIS). In real time, MS-TAMIS can differentiate rectal mucosa and submucosa based on their relative abundance of triglycerides and glycerophospholipids. The ex vivo accuracy distinguishing diseased and normal tissues is maintained in vivo at 90%, with negative predictive value of 95%. The system identified a deep and lateral involved tumour margin during TAMIS.
Conclusions
REIMS distinguishes rectal tissue types based on underlying lipid biology, and this can be translated in vivo by coupling it to TAMIS. There is a role for this technology in improving the efficacy of resection of early rectal cancers.
Background
Nipple discharge is the third most frequent complaint of women attending rapid diagnostic breast clinics. Nipple smear cytology remains the single most used diagnostic method for ...investigating fluid content. This study aimed to conduct a systematic review and meta-analysis of the diagnostic accuracy of nipple discharge fluid assessment.
Methods
The study incorporated searches for studies interrogating the diagnostic data of nipple discharge fluid cytology compared with the histopathology gold standard. Data from studies published from 1956 to 2019 were analyzed. The analysis included 8648 cytology samples of women with a presenting complaint of nipple discharge. Both hierarchical and bivariate models for diagnostic meta-analysis were used to attain overall pooled sensitivity and specificity.
Results
Of 837 studies retrieved, 45 fulfilled the criteria for inclusion. The diagnostic accuracy of the meta-analysis examining nipple discharge fluid had a sensitivity of 75 % (95 % confidence interval CI, 0.74–0.77) and a specificity of 87 % (95 % CI, 0.86–0.87) for benign breast disease. For breast cancer, it had a sensitivity of 62 % (95 % CI, 0.53–0.71) and a specificity 71 % (95 % CI, 0.57–0.81). Furthermore, patients presenting with blood-stained discharge yielded an overall malignancy rate of 58 % (95 % CI, 0.54–0.60) with a positive predictive value (PPV) of 27 % (95 % CI, 0.17–0.36).
Conclusions
Pooled data from studies encompassing nipple discharge fluid assessment suggest that nipple smear cytology is of limited diagnostic accuracy. The authors recommend that a tailored approach to diagnosis be required given the variable sensitivities of currently available tests.
Histopathological diagnosis of biopsy samples and margin assessment of surgical specimens are challenging aspects in sarcoma. Using dog patient tissues, we assessed the performance of a recently ...developed technology for fast ex vivo molecular lipid-based diagnosis of sarcomas. The instrument is based on mass spectrometry (MS) molecular analysis through a laser microprobe operating under ambient conditions using excitation of endogenous water molecules. Classification models based on cancer/normal/necrotic, tumor grade, and subtypes showed a minimum of 97.63% correct classification. Specific markers of normal, cancer, and necrotic regions were identified by tandem MS and validated by MS imaging. Real-time detection capabilities were demonstrated by ex vivo analysis with direct interrogation of classification models.
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•SpiderMass technology collects molecular information ex vivo and in vivo•Tumor classification by typing and grading is obtained by the technology•Found markers are cross-validated with mass spectrometry imaging•The technology was assessed ex vivo at the vet surgery room
Using dog tissue samples, Saudemont et al. evaluate the performance of a mass spectrometry-based analysis of lipids for fast ex vivo diagnosis of sarcomas. This approach may improve the clinical management of sarcomas by facilitating histopathological diagnosis of biopsy samples and surgical margin assessment.
Purpose
To calculate the diagnostic accuracy of nipple aspirate fluid (NAF) cytology.
Background
Evaluation of NAF cytology in asymptomatic patients conceptually offers a non-invasive method for ...either screening for breast cancer or else predicting or stratifying future cancer risk.
Methods
Studies were identified by performing electronic searches up to August 2019. A meta-analysis was conducted to attain an overall pooled sensitivity and specificity of NAF for breast cancer detection.
Results
A search through 938 studies yielded a total of 19 studies. Overall, 9308 patients were examined, with cytology results from 10,147 breasts age (years), mean ± SD = 49.73 ± 4.09 years. Diagnostic accuracy meta-analysis of NAF revealed a pooled specificity of 0.97 (95% CI 0.97–0.98), and sensitivity of 0.64 (95% CI 0.62–0.66).
Conclusions
The diagnostic accuracy of nipple smear cytology is limited by poor sensitivity. If nipple fluid assessment is to be used for diagnosis, then emerging technologies for fluid biomarker analysis must supersede the current diagnostic accuracy of NAF cytology.
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