Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer

Willemieke S. Tummers, Sarah E. Miller, Nutte T. Teraphongphom, Nynke S. van den Berg, Alifia Hasan, Teri A. Longacre, George A. Fisher, Bert A. Bonsing, Alexander L. Vahrmeijer, Sanjiv S. Gambhir, Rutger-Jan Swijnenburg, Eben L. Rosenthal, George A. Poultsides

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC). Methods: A dose-escalation prospective study was performed to assess feasibility of tumor detection within peripancreatic LNs using cetuximab-IRDye800 in PDAC patients. Fluorescent imaging of dissected LNs was analyzed ex vivo macroscopically and microscopically and fluorescence was correlated with histopathology. Results: A total of 144 LNs (72 in the low-dose and 72 in the high-dose cohort) were evaluated. Detection of metastatic LNs by fluorescence was better in the low-dose (50 mg) cohort, where sensitivity and specificity was 100% and 78% macroscopically, and 91% and 66% microscopically. More importantly, this method was able to detect occult foci of tumor (measuring < 5 mm) with a sensitivity of 88% (15/17 LNs). Conclusion: This study provides proof of concept that intraoperative fluorescent imaging with cetuximab-IRDye800 can facilitate the detection of peripancreatic lymph nodes often containing subclinical foci of disease.
Original languageEnglish
Pages (from-to)883-890
JournalHPB
Volume21
Issue number7
DOIs
Publication statusPublished - 1 Jul 2019

Cite this

Tummers, W. S., Miller, S. E., Teraphongphom, N. T., van den Berg, N. S., Hasan, A., Longacre, T. A., ... Poultsides, G. A. (2019). Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer. HPB, 21(7), 883-890. https://doi.org/10.1016/j.hpb.2018.11.008
Tummers, Willemieke S. ; Miller, Sarah E. ; Teraphongphom, Nutte T. ; van den Berg, Nynke S. ; Hasan, Alifia ; Longacre, Teri A. ; Fisher, George A. ; Bonsing, Bert A. ; Vahrmeijer, Alexander L. ; Gambhir, Sanjiv S. ; Swijnenburg, Rutger-Jan ; Rosenthal, Eben L. ; Poultsides, George A. / Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer. In: HPB. 2019 ; Vol. 21, No. 7. pp. 883-890.
@article{6f6bac41ece04eb2bceaca51a3094731,
title = "Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer",
abstract = "Background: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC). Methods: A dose-escalation prospective study was performed to assess feasibility of tumor detection within peripancreatic LNs using cetuximab-IRDye800 in PDAC patients. Fluorescent imaging of dissected LNs was analyzed ex vivo macroscopically and microscopically and fluorescence was correlated with histopathology. Results: A total of 144 LNs (72 in the low-dose and 72 in the high-dose cohort) were evaluated. Detection of metastatic LNs by fluorescence was better in the low-dose (50 mg) cohort, where sensitivity and specificity was 100{\%} and 78{\%} macroscopically, and 91{\%} and 66{\%} microscopically. More importantly, this method was able to detect occult foci of tumor (measuring < 5 mm) with a sensitivity of 88{\%} (15/17 LNs). Conclusion: This study provides proof of concept that intraoperative fluorescent imaging with cetuximab-IRDye800 can facilitate the detection of peripancreatic lymph nodes often containing subclinical foci of disease.",
author = "Tummers, {Willemieke S.} and Miller, {Sarah E.} and Teraphongphom, {Nutte T.} and {van den Berg}, {Nynke S.} and Alifia Hasan and Longacre, {Teri A.} and Fisher, {George A.} and Bonsing, {Bert A.} and Vahrmeijer, {Alexander L.} and Gambhir, {Sanjiv S.} and Rutger-Jan Swijnenburg and Rosenthal, {Eben L.} and Poultsides, {George A.}",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.hpb.2018.11.008",
language = "English",
volume = "21",
pages = "883--890",
journal = "HPB",
issn = "1477-2574",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

Tummers, WS, Miller, SE, Teraphongphom, NT, van den Berg, NS, Hasan, A, Longacre, TA, Fisher, GA, Bonsing, BA, Vahrmeijer, AL, Gambhir, SS, Swijnenburg, R-J, Rosenthal, EL & Poultsides, GA 2019, 'Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer' HPB, vol. 21, no. 7, pp. 883-890. https://doi.org/10.1016/j.hpb.2018.11.008

Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer. / Tummers, Willemieke S.; Miller, Sarah E.; Teraphongphom, Nutte T.; van den Berg, Nynke S.; Hasan, Alifia; Longacre, Teri A.; Fisher, George A.; Bonsing, Bert A.; Vahrmeijer, Alexander L.; Gambhir, Sanjiv S.; Swijnenburg, Rutger-Jan; Rosenthal, Eben L.; Poultsides, George A.

In: HPB, Vol. 21, No. 7, 01.07.2019, p. 883-890.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer

AU - Tummers, Willemieke S.

AU - Miller, Sarah E.

AU - Teraphongphom, Nutte T.

AU - van den Berg, Nynke S.

AU - Hasan, Alifia

AU - Longacre, Teri A.

AU - Fisher, George A.

AU - Bonsing, Bert A.

AU - Vahrmeijer, Alexander L.

AU - Gambhir, Sanjiv S.

AU - Swijnenburg, Rutger-Jan

AU - Rosenthal, Eben L.

AU - Poultsides, George A.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC). Methods: A dose-escalation prospective study was performed to assess feasibility of tumor detection within peripancreatic LNs using cetuximab-IRDye800 in PDAC patients. Fluorescent imaging of dissected LNs was analyzed ex vivo macroscopically and microscopically and fluorescence was correlated with histopathology. Results: A total of 144 LNs (72 in the low-dose and 72 in the high-dose cohort) were evaluated. Detection of metastatic LNs by fluorescence was better in the low-dose (50 mg) cohort, where sensitivity and specificity was 100% and 78% macroscopically, and 91% and 66% microscopically. More importantly, this method was able to detect occult foci of tumor (measuring < 5 mm) with a sensitivity of 88% (15/17 LNs). Conclusion: This study provides proof of concept that intraoperative fluorescent imaging with cetuximab-IRDye800 can facilitate the detection of peripancreatic lymph nodes often containing subclinical foci of disease.

AB - Background: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC). Methods: A dose-escalation prospective study was performed to assess feasibility of tumor detection within peripancreatic LNs using cetuximab-IRDye800 in PDAC patients. Fluorescent imaging of dissected LNs was analyzed ex vivo macroscopically and microscopically and fluorescence was correlated with histopathology. Results: A total of 144 LNs (72 in the low-dose and 72 in the high-dose cohort) were evaluated. Detection of metastatic LNs by fluorescence was better in the low-dose (50 mg) cohort, where sensitivity and specificity was 100% and 78% macroscopically, and 91% and 66% microscopically. More importantly, this method was able to detect occult foci of tumor (measuring < 5 mm) with a sensitivity of 88% (15/17 LNs). Conclusion: This study provides proof of concept that intraoperative fluorescent imaging with cetuximab-IRDye800 can facilitate the detection of peripancreatic lymph nodes often containing subclinical foci of disease.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85060857449&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30723062

U2 - 10.1016/j.hpb.2018.11.008

DO - 10.1016/j.hpb.2018.11.008

M3 - Article

VL - 21

SP - 883

EP - 890

JO - HPB

JF - HPB

SN - 1477-2574

IS - 7

ER -