A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis

Abstract Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with...

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Autores principales: Emmanuel M. Gabriel, Minhyung Kim, Daniel T. Fisher, Catherine Mangum, Kristopher Attwood, Wenyan Ji, Debabrata Mukhopadhyay, Sanjay P. Bagaria, Matthew W. Robertson, Tri A. Dinh, Keith L. Knutson, Joseph J. Skitzki, Michael B. Wallace
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spelling oai:doaj.org-article:8b34f51c24a64fa09479af59322079482021-12-02T13:20:14ZA pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis10.1038/s41598-021-84430-32045-2322https://doaj.org/article/8b34f51c24a64fa09479af59322079482021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84430-3https://doaj.org/toc/2045-2322Abstract Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).Emmanuel M. GabrielMinhyung KimDaniel T. FisherCatherine MangumKristopher AttwoodWenyan JiDebabrata MukhopadhyaySanjay P. BagariaMatthew W. RobertsonTri A. DinhKeith L. KnutsonJoseph J. SkitzkiMichael B. WallaceNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Emmanuel M. Gabriel
Minhyung Kim
Daniel T. Fisher
Catherine Mangum
Kristopher Attwood
Wenyan Ji
Debabrata Mukhopadhyay
Sanjay P. Bagaria
Matthew W. Robertson
Tri A. Dinh
Keith L. Knutson
Joseph J. Skitzki
Michael B. Wallace
A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
description Abstract Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).
format article
author Emmanuel M. Gabriel
Minhyung Kim
Daniel T. Fisher
Catherine Mangum
Kristopher Attwood
Wenyan Ji
Debabrata Mukhopadhyay
Sanjay P. Bagaria
Matthew W. Robertson
Tri A. Dinh
Keith L. Knutson
Joseph J. Skitzki
Michael B. Wallace
author_facet Emmanuel M. Gabriel
Minhyung Kim
Daniel T. Fisher
Catherine Mangum
Kristopher Attwood
Wenyan Ji
Debabrata Mukhopadhyay
Sanjay P. Bagaria
Matthew W. Robertson
Tri A. Dinh
Keith L. Knutson
Joseph J. Skitzki
Michael B. Wallace
author_sort Emmanuel M. Gabriel
title A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
title_short A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
title_full A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
title_fullStr A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
title_full_unstemmed A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
title_sort pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/8b34f51c24a64fa09479af5932207948
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