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Interstitial hypertension in human breast and colorectal tumors
J R Less1, M C Posner, Y Boucher
1Department of Surgery, University of Pittsburgh, Pennsylvania.
Abstract:
The efficacy of present day antineoplastic regimens depends upon the delivery and penetration of therapeutic agents through the tumor vascular and interstitial spaces to the tumor cell target. The distribution of relevant molecules or cells in a solid tumor is often poor and heterogeneous and is believed to be due to a number of pathophysiological factors, including elevated interstitial fluid pressure (IFP). Using the wick-in-needle technique, IFP was measured in primary breast and colorectal carcinomas as well as their respective metastases to the lymph nodes and liver in a total of 17 patients. IFP was also measured in one recurrent renal cell carcinoma, one melanoma metastasis to the lymph nodes, and another melanoma metastasis to the lung. IFP varied from 4 to 50 mm Hg with a mean +/- SD of 20 +/- 13 mm Hg in the neoplasms (n = 41 measurements; n = 21 tumors), while IFP in normal tissues had a mean of 2 +/- 4 mm Hg (n = 11). The mean IFPs for metastatic melanoma, primary breast carcinoma, and liver metastases from a colorectal primary were found to be 33 +/- 14, 15 +/- 9, and 21 +/- 12 mm Hg, respectively. In the renal cell carcinoma, the pressure was 38 mm Hg. These results agree with the findings of our 3 previous studies examining IFP in human superficial melanomas (14.3 +/- 12.5 mm Hg, n = 12), cervical carcinomas (15.7 +/- 5.7 mm Hg, n = 12), and head and neck tumors (13.2 +/- 8.8 mm Hg, n = 19), and indicate that in all types of human tumors studied to date, IFP was significantly elevated above that of normal tissue. This observation may be useful in localizing tumors during needle biopsy.
Insights
Elevated interstitial fluid pressure (IFP) in tumors hinders cancer drug delivery. This study measured IFP in various human cancers, finding it significantly higher than in normal tissues, suggesting a potential role in tumor localization for biopsies.
Area of Science:
- Oncology
- Biomedical Engineering
- Pathophysiology
Background:
- Antineoplastic drug efficacy relies on effective delivery to tumor cells.
- Poor drug distribution in solid tumors is linked to elevated interstitial fluid pressure (IFP).
Purpose of the Study:
- To measure interstitial fluid pressure (IFP) in various human tumors.
- To compare tumor IFP with normal tissue IFP.
- To assess the potential of IFP measurements in tumor localization.
Main Methods:
- Wick-in-needle technique used to measure IFP.
- IFP measured in primary breast, colorectal, renal cell carcinomas, and melanoma metastases.
- IFP also measured in lymph node and liver metastases, and normal tissues for comparison.
Main Results:
- Tumor IFP ranged from 4 to 50 mm Hg (mean 20 +/- 13 mm Hg), significantly higher than normal tissue (mean 2 +/- 4 mm Hg).
- Elevated IFP observed across all measured tumor types, including breast, colorectal, renal cell carcinoma, and melanoma.
- Specific mean IFPs: metastatic melanoma (33 +/- 14 mm Hg), primary breast carcinoma (15 +/- 9 mm Hg), colorectal liver metastases (21 +/- 12 mm Hg), renal cell carcinoma (38 mm Hg).
Conclusions:
- Interstitial fluid pressure (IFP) is significantly elevated in all human tumors studied compared to normal tissues.
- This consistent elevation of IFP across tumor types may offer a novel approach for tumor localization during needle biopsy procedures.