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Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging.

ABSTRACT: Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections of) the tissue at the resected specimen margin(s) to verify whether cancer is present. We compare this method to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 banked human cancerous and normal gastric-tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, here, the Lasso method (which stands for least absolute shrinkage and selection operator and which is a multiclass logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The methodology developed with 28 frozen training samples of clear histopathologic diagnosis showed an overall accuracy value of 98% for the 12,480 pixels evaluated in cross-validation (CV), and 97% when a completely independent set of samples was tested. By applying an additional spatial smoothing technique, the accuracy for both CV and the independent set of samples was 99% compared with histological diagnoses. To test our method for clinical use, we applied it to a total of 21 tissue-margin samples prospectively obtained from nine gastric-cancer patients. The results obtained suggest that DESI-MSI/Lasso may be valuable for routine intraoperative assessment of the specimen margins during gastric-cancer surgery.

SUBMITTER: Eberlin LS

PROVIDER: S-EPMC3932851 | biostudies-other | 2014 Feb

REPOSITORIES: biostudies-other

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Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging.

Eberlin Livia S LS Tibshirani Robert J RJ Zhang Jialing J Longacre Teri A TA Berry Gerald J GJ Bingham David B DB Norton Jeffrey A JA Zare Richard N RN Poultsides George A GA

Proceedings of the National Academy of Sciences of the United States of America 20140203 7

Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections of) the tissue at the resected specimen margin(s) to verify whether cancer is present. We compare this method to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 banked human cancerous and normal gastric-tissue samples. In DESI-MSI, microdroplets strike ...[more]

PMID: 24550265

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Project description:BackgroundSurgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery.Methods and findingsOur methodology was developed and tested using 63 banked pancreatic cancer samples and 65 samples (tumor and specimen margins) collected prospectively during 32 pancreatectomies from February 27, 2013, to January 16, 2015. In total, mass spectra for 254,235 individual pixels were evaluated. When cross-validation was employed in the training set of samples, 98.1% agreement with histopathology was obtained. Using an independent set of samples, 98.6% agreement was achieved. We used a statistical approach to evaluate 177,727 mass spectra from samples with complex, mixed histology, achieving an agreement of 81%. The developed method showed agreement with frozen section evaluation of specimen margins in 24 of 32 surgical cases prospectively evaluated. In the remaining eight patients, margins were found to be positive by DESI-MSI/Lasso, but negative by frozen section analysis. The median overall survival after resection was only 10 mo for these eight patients as opposed to 26 mo for patients with negative margins by both techniques. This observation suggests that our method (as opposed to the standard method to date) was able to detect tumor involvement at the margin in patients who developed early recurrence. Nonetheless, a larger cohort of samples is needed to validate the findings described in this study. Careful evaluation of the long-term benefits to patients of the use of DESI-MSI for surgical margin evaluation is also needed to determine its value in clinical practice.ConclusionsOur findings provide evidence that the molecular information obtained by DESI-MSI/Lasso from pancreatic tissue samples has the potential to transform the evaluation of surgical specimens. With further development, we believe the described methodology could be routinely used for intraoperative surgical margin assessment of pancreatic cancer.

Project description:ImportanceIntraoperative consultation (IOC) on surgical margins during curative intent resection of gastric and gastroesophageal adenocarcinoma presents sampling and interpretive challenges. A false-negative (FN) IOC result can affect clinical care. Many factors may be associated with higher risk for an FN result of IOC on surgical margins.ObjectiveTo assess the prevalence and clinical implications of FN results of IOC on surgical margins during resection of gastric and gastroesophageal adenocarcinoma.Design, setting, and participantsThis retrospective study assessed the results of IOC on surgical margins to determine the prevalence of FN results and the accuracy and clinical implications of the results for patients undergoing curative intent resection for gastric or gastroesophageal adenocarcinoma. The study examined patients with gastric or gastroesophageal adenocarcinoma who underwent resection with curative intent at a single-institution referral center from January 1, 1992, to December 31, 2015.InterventionsCurative intent gastric and/or esophageal resection.Main outcomes and measuresFalse-negative results of IOC on surgical margins, accuracy of the results, factors associated with decreased accuracy of the results, and clinical implications of FN results.ResultsThis study included 2002 patients (median age, 65 years; 1343 [67.1%] male; 1638 [81.8%] white) who received 3171 IOCs on surgical margins. Of the 3171 IOCs, the prevalence of FN results was 1.7%, with an accuracy of 98.1%. The prevalence of an FN IOC result was 1.2% for esophageal margins, 2.0% for gastric margins, and 2.5% for duodenal margins (P = .04). The prevalence of an FN IOC result was higher for patients with diffuse or signet ring disease compared with those without (2.6% vs 1.2%, P = .002) and for those not receiving neoadjuvant radiotherapy compared with those receiving neoadjuvant radiotherapy (1.4% vs 0.7%, P < .001). The prevalence of FN results of IOCs performed by nongastrointestinal pathologists was similar to that of IOCs performed by gastrointestinal pathologists (2.3% vs 1.9%, P = .60). The disease-specific survival was 34 months (95% CI, 20.7-47.2 months) for those with an FN result and 26.9 months (95% CI, 18.3-35.4; P = .72) for those with a true-positive result. Half of the patients with FN IOC results received further margin-directed therapy, including subsequent resection or radiotherapy.Conclusions and relevanceThis study found that IOC on surgical margins was accurate at a specialty center. Signet ring or diffuse disease, duodenal margins, and not receiving neoadjuvant radiotherapy were challenging scenarios for IOC on surgical margins. The use of IOC on surgical margins may be optimal when it will affect intraoperative decision making framed by the stage of disease, tumor location, and surgical fitness of the patient.

Project description:BackgroundRadical gastrectomy is the cornerstone of the treatment of locally advanced gastric cancer. This study was designed to evaluate factors associated with a tumor-positive resection margin after gastrectomy and to evaluate the influence of hospital volume.MethodsIn this Dutch cohort study, patients with junctional or gastric cancer who underwent curative gastrectomy between 2011 and 2017 were included. The primary outcome was incomplete tumor removal after the operation defined as the microscopic presence of tumor cells at the resection margin. The association of patient and disease characteristics with incomplete tumor removal was tested with multivariable regression analysis. The association of annual hospital volume with incomplete tumor removal was tested and adjusted for the patient- and disease characteristics.ResultsIn total, 2799 patients were included. Incomplete tumor removal was seen in 265 (9.5%) patients. Factors associated with incomplete tumor removal were: tumor located in the entire stomach (odds ratio (OR) [95% confidence interval (CI): 3.38 [1.91-5.96] reference: gastroesophageal junction), cT3, cT4, cTx (1.75 [1.20-2.56], 2.63 [1.47-4.70], 1.60 [1.03-2.48], reference: cT0-2), pN+ (2.73 [1.96-3.80], reference: pN-), and diffuse and unknown histological subtype (3.15 [2.14-4.46] and 2.05 [1.34-3.13], reference: intestinal). Unknown differentiation grade was associated with complete tumor removal (0.50 [0.30-0.83], reference: poor/undifferentiated). Compared with a hospital volume of <?20 resections/year, 20-39, and >?39 resections were associated with lower probability for incomplete tumor removal (OR 0.56 [0.42-0.76] and 0.34 [0.18-0.64]).ConclusionsTumor location, cT, pN, histological subtype, and tumor differentiation are associated with incomplete tumor removal. The association of incomplete tumor removal with an annual hospital volume of <?20 resections may underline the need for further centralization of gastric cancer care in the Netherlands.

Dataset Information

Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging.

Publications

Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging.

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