Thermal heterogeneity constitutes a marker for the detection of malignant solid lesions, in vivo

Abstract
The aim of this study was to investigate the existence of any thermal difference between malignant tumors and inflammatory benign lesions of the human and to determine whether it correlates with tumor angiogenesis quantification. In order to test this hypothesis a new in vivo, method, was developed in our institute, based on a thermography catheter. We calculated the differences of the temperature of the solid tumor and of a normal area (DT). In the "urinary bladder" project 8 patients had benign tumor (40%) and 12 had malignant tumor (60%), according the biopsy histology. We found significant differences of DT between patients with benign and malignant tumor (P-value < 0.001). Also, differences were found for the mean values of angiogenesis level between malignant and benign tumors (P-value = 0.0261) and a moderated positive correlation was estimated between the degree of angiogenesis and DT (P-value = 0.02). Based on logistic regression analysis we found that one-degree increase of DT triples the odds of a patient having a malignant tumor [OR = 2.91; 95% CI, 1.97 to 7.78; P-value < 0.001], adjusted for the degree of angiogenesis (P-value = 0.0236) and the grade of tumor (P-value < 0.001). A threshold point of DT = 0.7 °C was determined, with sensitivity 83% and specificity 75%. Similar results, regarding the association between DT and malignancy, were observed in the "upper gastrointestinal" and "lung" projects. These findings suggest that the calculated difference of temperature between normal tissue and neoplastic area could be a useful criterion in the diagnosis of malignancy in tumors.

Key words
Thermography, malignancy

Bibliografía del artículo

1. Feldmann HJ, Molls M, Vaupel P: Blood flow and oxygenation status of human tumors. Clinical investigations. Strahlentker Onkol 175:1-9, 1999
2. Dickinson AJ, Fox SB, Persad RA, et al: Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas. Br J Urol 74:762-766, 1994.
3. Philp EA, Stephenson TJ, Reed MWR: Prognostic significance of angiogenesis in transitional cell carcinoma of the human urinary bladder. Br J Urol 77:352-357, 1996
4. Isner JM: Cancer and atherosclerosis. The broad mandate of angiogenesis. Circulation 99:1653-1655, 1999
5. Luo CY, Ko WC, Tsao CJ, et al: Epstein-Barr virus-containing T-cells lymphoma and artherosclerotic abdominal aortic aneurysm in a young adult. Hum Pathol 30:1114-1117, 1999
6. Arnold F: Exploiting angiogenesis. The Lancet 337:865-866, 1991
7. Malonne H, Langer I, Kiss R, et al: Mechanisms of tumor angiogenesis and therapeutic implications: angiogenesis inhibitors. Clin Exp Metastasis 17:1-14,1999
8. Weidner N, Semple JP, Welch WR, et al: Tumor angiogenesis and metastasis-correlation in invasive carcinoma. N Engl J Med 324:1-8, 1991
9. Meitar D, Crawford SE, Rademaker AW, et al: Tumor angiogenesis correlates with metastatic disease, N-myc amplification, and poor outcome in human neuroblastoma. J Clin Oncol 14:405-414, 1996
10. Canete A, Navarro S, Bermudez J, Pellin A, Castel V, Llombart-Bos: Angiogenesis in neuroblastoma :relatioship to survival and prognostic factors in a cohort of neuroblastoma patients J Clin Oncol 2000 Jan;18(1):27-34
11. Crew JP, O'Brien T, Bradburn M, et al: Vascular endothelial growth factor is a predictor of relapse stage progression in superficial bladder cancer. Cancer Res 57:5281-5285, 1997
12. Edell Sl, Eisen MD: Current imaging modalities for the diagnosis of breast cancer. Del Med J 71:377-382, 1999
13. Head JF, Elliott RL: Thermography. Its relation to pathologic characteristics, vascularity, proliferation rate, and survival of patients with invasive ductal carcinoma of the breast. Cancer 79:186-188, 1999
14. Beldermann SC, Frey H, Reinhardt S, et al: Diagnosis of blood flow in breast rumors with increased blood pressure. New possibility in tumor field diagnosis. Radiology 37:643-650, 1997
15. Gasparini G, Harris AL Clinical importance of the determination of tumor angiogenesis in breast carcinoma: much more than a new prognostic tool J Clin Onvol 1995;13(3):765-82
16. Koss LG, Melamed MR, Ricci A, et al: Carcinogenesis in human urinary bladder: Observation after exposure to para-aminodiphenyl. N Engl J Med 272:767-770, 1965
17. Fukui I, Yokokawa M, Mitani G: In vivo staining test with methylene blue for bladder cancer. J Urol 130:252-255, 1983
18. Devonec M, Lenz P, Bouvier R, et al: Clinically occult bladder cancer diagnosis, Trial using ultraviolet cystoscopy. Cancer 55:468-471, 1985
19. Stefanadis C, Chrysochoou C, Markou D, Petraki K, Panagiotakos DB, Fasoulakis C, Kyriakidis A, Papadimitriou C, Toutouzas PK. Increased temperature of malignant urinary bladder tumors, in vivo; the application of a new method based on a catheter technique. J Clin Oncol. 2001; 19(3): 676-681.
20. Stefanadis C, Chrysohoou C, Paraskevas E, Panagiotakos DB, Xynopoulos D, Dimitroulopoulos D, Petraki K, Papadimitriou C, Karoutsos K, Pitsavos C, Toutouzas PK. Thermal Heterogeneity Constitutes A Marker For The Detection Of Malignant Gastric Lesions, In Vivo. J Clin Gastroenterology 2003; (in press)
21. Stefanadis C, Toutouzas P: In vivo local thermography of coronary artery atherosclerotic plaques in humans. Ann Intern Med 129:1079-1080, 1998
22. Stefanadis C, Diamantopoulos L, Vlachopoulos C, et al: Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo. Circulation 99:1965-1971, 1999
23. World Health Organization. Histological Typing of Urinary Bladder Tumors. International Classification of Tumors. Geneva: WHO, 1973.
24. Fukui I, Yokokawa M, Mitani G: In vivo staining test with methylene blue for bladder cancer. J Urol 130:252-255, 1983.
25. Devonec M, Lenz P, Bouvier R, et al: Clinically occult bladder cancer diagnosis, Trial using ultraviolet cystoscopy. Cancer 55:468-471, 1985.
26. Shahabuddin S, Arnold F, Costello CB, et al: Tumor angiogenesis factor in urological cancers. Br J Urol 56:490-494, 1984.