The success of coupling noninvasive monitoring with key nutrition provides a robust basis for tailoring intervention to an individual. This system provides a reliable evaluation of each person on a case-by-case criterion. Thus we are able to evaluate the individual’s ability to respond to nutritional and life-style intervention, and the potential need for more invasive medical intervention and treatment, while reducing unnecessary invasive treatments.
ADVANCES IN CANCER IMAGING
Background & Brief History
In 1940, the classic textbook of pathology, Ewing’s Neoplastic Diseases1 noted that PCa is a rare disease, accounting for 2.7 % of tumors in the male population of that era. Half a century ago, pathologists found a high percentage of men without “clinical” PCa to have malignant cells in the operative specimens of surgery for relief of benign prostatic obstruction. In addition, the rate of cancer being present in prostates examined during autopsy varies dramatically in different regions of the world, with the food supply being the single variable able to account for the differences. In the absence of demonstrable tumor invasion, perhaps cancer formation should be considered a non-threatening aspect of normal body aging, or at worst, a chronic disease that is governed by lifestyle and the available food supply.
This leads to a simple clinical question: Is there a way to determine whether a cancer is part of the natural aging process to be watched (inconsequential cancer) or whether the malignancy will have deadly consequences?
This question is being answered by a building body of knowledge that has recently been accelerated by technological advances in diagnostic imaging. In 1985, a prominent British physician, David Cosgrove, published a paper in the American Journal of Radiology demonstrating the presence of blood flows in breast cancers. The new generation of sonogram equipment had the capability to show pictures of blood vessels. The arteries and veins supplying a tumor could be clearly imaged. Moreover, the actual flowing blood in the cancer could be seen and velocity of flow of blood in the vessels accurately measured. At an international conference in Italy in 1997, Dr. Rodolfo Campani, an Italian radiologist specializing in studying the blood flows of cancers at the University of Pavia Medical Center, showed the criteria to differentiate malignant cancer vessels from benign tumor blood vessels. Benign vessels are few in number, smoothly outlined, follow straight courses and branch regularly. Malignant vessels are many in number, irregularly outlined, irregular in course and crooked in branching patterns. These findings have been confirmed by other investigators, and presented at the 2006 World Congress of Interventional Oncology. Today, malignant blood vessels may be accurately and noninvasively detected by newer Doppler sonography techniques and advanced blood flow MRI protocols.
Sonography
Doppler Ultrasound has Wide Applications for Improving Cancer Therapy
The physical principle of ultrasound, the piezoelectric effect where sound is created from electrical energy, was discovered by Pierre and Marie Curie ten years before the recognition of the X-Ray. Early medical uses included imaging disorders of the eye, heart, and the developing fetus. As computers grew in sophistication, so did the applications of ultrasound, and now, it is often used as the first diagnostic test for many medical disorders. Doppler sonar, created in 1972, gives pictures of flow movement in the human body in the same way it shows motion in the weather patterns (Doppler radar) that one sees on television weather reports. Doppler technology has been around for years.
Urologists in Japan, oncologists in England, surgeons in the Netherlands, chemotherapists in Belgium, ultrasonographers in Norway, and radiologists in France, seeing the success of sonograms in diagnosing malignant tumors in the breast, turned their attention to the study of the prostate. They concluded that the vascular pattern shown by the Doppler technique held the key to the degree of malignancy. In 2002, German surgeons at the University of Ulm, the largest bone tumor center in Europe, showed bone cancers that were highly malignant had high blood flows. The current clinical use of Doppler equipment in Europe is keeping patients from unnecessarily losing their arms and legs to surgery. Historically, the standard treatment for bone cancer has been amputation of the entire limb; current surgical intervention has become more conservative, often removing a limited portion of the bone so the tumor can be removed with a rim of normal bone without the need for an amputation. However, by distinguishing cancer aggressiveness, Doppler techniques have refined this even more, since bone tumors that demonstrate no vascularity or low blood flows are now watched or treated more conservatively.
Dr. Nathalie Lassau, an interventional radiologist at the Institute de Cancerologie Gustav Roussy, an internationally known cancer center in Paris, published similar findings on the deadly skin cancer, melanoma. Her article in the American Journal of Radiology in 20022 revealed lethal skin cancers to be highly vascular and skin cancers that could be watched were not vascular. Dr. Lassau is currently investigating medicines to reduce blood flows to cancers in hope of lessening their malignant consequences and has presented this work at numerous international meetings. Her finding that 3D Doppler sonography correlates best with the pathologic process was highlighted at the 2011, Eighth International Symposium on Melanoma. Now, newer MRI imaging protocols are currently being fine-tuned based on the proven high accuracy of the Doppler sonography data.
Clinical Application of 3-D Doppler
•Imaging aggressiveness: The blood flow patterns depicted by Doppler sonography provide a way to quantitatively measure and serially monitor the severity of malignancy, as well as the response to therapy throughout the treatment course. Blood flow analysis can show which cancers are aggressive, since these have many vessels and which are responding to treatment, or nutritional intervention, or both, since the number of tumor vessels decreases with successful therapies.3
•Monitoring intervals: Because it is a non-invasive procedure, the 3-D Doppler exam can be performed as often as necessary. Our experience has shown that cancers are more variable in their response to intervention than generally believed. During early stages of diagnosis and intervention for PCa, a 3-month follow-up exam is warranted. Once the cancer shows signs of regressing, based primarily on measures of vascularity and density, a 6 to 9-month follow-up schedule is more appropriate. MRIs should be repeated when the tumor has not responded to treatment by 6-months. Routine ultrasound follow up should be on a 6-month basis and MRI yearly for 3-years.
•Tumor size alone can be misleading: The routine use of tumor size decrease has been shown to be less reliable than blood flow analysis, since the edema of cell death may cause dying cancers to enlarge. Although this concept was described in the early 1990’s in Europe, it was first mentioned in the American literature in 1996 at the American Roentgen Ray Society Annual Meeting. Dr. E. Louvar from the Henry Ford Hospital combined radiology and pathology studies to determine that the power Doppler flows in malignancies was related to the vessels that fed aggressive tumors.
•Highly correlated to Gleason scores: Significantly higher Gleason scores were seen in cancer biopsies of high Doppler flow areas compared to cancers with no Doppler flows. Dr. D. Downey at John Robarts Research Institute of the University Hospital in Ontario, Canada has looked at vascular imaging techniques and 3-D imaging of blood vessels. Blood vessels can be rendered in 3-D with angiography (high intensity dye injected into arteries), CT scanning (medium intensity dye), MR angiography (low intensity dye), 3-D color Doppler imaging, and 3-D power Doppler imaging. In this article, published from the American Journal of Radiology in 1995, he noted that in PCa power