Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging.
<h4>Background</h4>Surgical 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 f...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-08-01
|
| Series: | PLoS Medicine |
| Online Access: | https://doi.org/10.1371/journal.pmed.1002108 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850127249126195200 |
|---|---|
| author | Livia S Eberlin Katherine Margulis Ivette Planell-Mendez Richard N Zare Robert Tibshirani Teri A Longacre Moe Jalali Jeffrey A Norton George A Poultsides |
| author_facet | Livia S Eberlin Katherine Margulis Ivette Planell-Mendez Richard N Zare Robert Tibshirani Teri A Longacre Moe Jalali Jeffrey A Norton George A Poultsides |
| author_sort | Livia S Eberlin |
| collection | DOAJ |
| description | <h4>Background</h4>Surgical 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.<h4>Methods and findings</h4>Our 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.<h4>Conclusions</h4>Our 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. |
| format | Article |
| id | doaj-art-eb971e4c2cf945cba3318ffb66da574e |
| institution | OA Journals |
| issn | 1549-1277 1549-1676 |
| language | English |
| publishDate | 2016-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj-art-eb971e4c2cf945cba3318ffb66da574e2025-08-20T02:33:43ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762016-08-01138e100210810.1371/journal.pmed.1002108Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging.Livia S EberlinKatherine MargulisIvette Planell-MendezRichard N ZareRobert TibshiraniTeri A LongacreMoe JalaliJeffrey A NortonGeorge A Poultsides<h4>Background</h4>Surgical 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.<h4>Methods and findings</h4>Our 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.<h4>Conclusions</h4>Our 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.https://doi.org/10.1371/journal.pmed.1002108 |
| spellingShingle | Livia S Eberlin Katherine Margulis Ivette Planell-Mendez Richard N Zare Robert Tibshirani Teri A Longacre Moe Jalali Jeffrey A Norton George A Poultsides Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging. PLoS Medicine |
| title | Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging. |
| title_full | Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging. |
| title_fullStr | Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging. |
| title_full_unstemmed | Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging. |
| title_short | Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging. |
| title_sort | pancreatic cancer surgical resection margins molecular assessment by mass spectrometry imaging |
| url | https://doi.org/10.1371/journal.pmed.1002108 |
| work_keys_str_mv | AT liviaseberlin pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging AT katherinemargulis pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging AT ivetteplanellmendez pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging AT richardnzare pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging AT roberttibshirani pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging AT terialongacre pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging AT moejalali pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging AT jeffreyanorton pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging AT georgeapoultsides pancreaticcancersurgicalresectionmarginsmolecularassessmentbymassspectrometryimaging |