Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens.

Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins. Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software. Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6-110) vs. 48.3 (39.0-59.4), p = 0.002] and with chemotherapy [67.9 (54.6-89.2) vs. 48.6 (28.8-82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies. In summary, our study demonstrated real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.

Probe electrospray ionization mass spectrometry-based rapid diagnosis of liver tumors.

BACKGROUND AND AIM: Prompt differential diagnosis of liver tumors is clinically important and sometimes difficult. A new diagnostic device that combines probe electrospray ionization-mass spectrometry (PESI-MS) and machine learning may help provide the differential diagnosis of liver tumors. METHODS: We evaluated the diagnostic accuracy of this new PESI-MS device using tissues obtained and stored from previous surgically resected specimens. The following cancer tissues (with collection dates): hepatocellular carcinoma (HCC, 2016-2019), intrahepatic cholangiocellular carcinoma (ICC, 2014-2019), and colorectal liver metastasis (CRLM, 2014-2019) from patients who underwent hepatic resection were considered for use in this study. Non-cancerous liver tissues (NL) taken from CRLM cases were also incorporated into the analysis. Each mass spectrum provided by PESI-MS was tested using support vector machine, a type of machine learning, to evaluate the discriminatory ability of the device. RESULTS: In this study, we used samples from 91 of 139 patients with HCC, all 24 ICC samples, and 103 of 202 CRLM samples; 80 NL from CRLM cases were also used. Each mass spectrum was obtained by PESI-MS in a few minutes and was evaluated by machine learning. The sensitivity, specificity, and diagnostic accuracy of the PESI-MS device for discriminating HCC, ICC, and CRLM from among a mix of all three tumors and from NL were 98.9%, 98.1%, and 98.3%; 87.5%, 93.1%, and 92.6%; and 99.0%, 97.9%, and 98.3%, respectively. CONCLUSION: This study demonstrated that PESI-MS and machine learning could discriminate liver tumors accurately and rapidly.

A new rapid diagnostic system with ambient mass spectrometry and machine learning for colorectal liver metastasis.

BACKGROUND: Probe electrospray ionization-mass spectrometry (PESI-MS) can rapidly visualize mass spectra of small, surgically obtained tissue samples, and is a promising novel diagnostic tool when combined with machine learning which discriminates malignant spectrum patterns from others. The present study was performed to evaluate the utility of this device for rapid diagnosis of colorectal liver metastasis (CRLM). METHODS: A prospectively planned study using retrospectively obtained tissues was performed. In total, 103 CRLM samples and 80 non-cancer liver tissues cut from surgically extracted specimens were analyzed using PESI-MS. Mass spectra obtained by PESI-MS were classified into cancer or non-cancer groups by using logistic regression, a kind of machine learning. Next, to identify the exact molecules responsible for the difference between CRLM and non-cancerous tissues, we performed liquid chromatography-electrospray ionization-MS (LC-ESI-MS), which visualizes sample molecular composition in more detail. RESULTS: This diagnostic system distinguished CRLM from non-cancer liver parenchyma with an accuracy rate of 99.5%. The area under the receiver operating characteristic curve reached 0.9999. LC-ESI-MS analysis showed higher ion intensities of phosphatidylcholine and phosphatidylethanolamine in CRLM than in non-cancer liver parenchyma (P < 0.01, respectively). The proportion of phospholipids categorized as monounsaturated fatty acids was higher in CRLM (37.2%) than in non-cancer liver parenchyma (10.7%; P < 0.01). CONCLUSION: The combination of PESI-MS and machine learning distinguished CRLM from non-cancer tissue with high accuracy. Phospholipids categorized as monounsaturated fatty acids contributed to the difference between CRLM and normal parenchyma and might also be a useful diagnostic biomarker and therapeutic target for CRLM.

Assessment of Preoperative Liver Function for Surgical Decision Making in Patients with Hepatocellular Carcinoma.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) have underlying liver disease and a preoperative liver function evaluation is important to avoid postoperative liver failure and death. In Western guidelines, portal hypertension (PH) is listed as a contraindication for liver resection. On the other hand, the indocyanine green retention rate at 15 min (ICG R15) has been widely used in Asian countries for surgical decision making. However, these criteria are based on reports published in the 20th century that included only a small number of patients and were developed empirically. SUMMARY: The number of published case series concerning liver resection in HCC patients with PH has been rapidly increasing since 2011, indicating that liver resection in HCC patients with PH is now routinely performed in specialized centers worldwide. Although PH certainly has an impact and should be considered as a contraindication for major liver resection, it is no longer considered to be a contraindication for minor liver resection, especially laparoscopic liver resection. In addition, new biomarkers and imaging tools to assess preoperative liver function have been extensively reported. The combination of these new factors to well-known risk factors, such as PH and ICG R15, might strengthen the ability to stratify the risk of postoperative liver failure. KEY MESSAGES: The present review covers recent topics regarding the assessment of preoperative liver function for surgical decision making in patients with HCC.