Views
6 months ago

AD 2016 Q1

RESEARCH, EDUCATION &

RESEARCH, EDUCATION & MEDICINE EXPERT OPINIONS Genetic testing facilitates precision medicine, which has improved breast cancer treatment. Decompression sickness, like breast cancer, may be promoted by particular genetic or epigenetic variables, which if better understood could lead to precision medicine for divers. The Future of Dive Medicine HOW SCIENTIFIC RESEARCH WILL ENHANCE DIVER SAFETY By Petar Denoble, M.D., D.S.C. ERAXION/ISTOCCKPHOTO.COM Medical advances in recent decades have led to targeted treatments for some cancers. This has raised hopes for similar breakthroughs in the fights against other diseases. Politicians are getting involved, calling for further work in “precision medicine” and individualized approaches to patients. Medicine in the 20th century identified specific causes and treatments for many diseases, but treatment outcomes remain highly variable. We have learned that most diseases and injuries are caused by multiple factors, meaning that a specific event, condition or individual characteristic by itself is not generally sufficient to produce the disease. When our knowledge of any of the integral factors of a given disease is incomplete, we remain puzzled by varying outcomes, and our preventive and treatment interventions lack desirable precision and efficacy. Sometimes unbeknownst to us there are several different sets of causal mechanisms that can lead to a specific disease. Other times individuals’ responses to a known set of causal factors remain variable for unknown reasons. Advances in genomic studies open new possibilities for identifying causes of variability — both in responses to harmful factors and in the efficacy of specific treatments. This has advanced modern oncology, and a similar approach could benefit other areas of medicine, too. First we will examine how genetic testing enables precision medicine in two common cancers, breast cancer and lung cancer, then we will discuss how precision medicine pertains to dive medicine. Breast cancer provides a good example of how genetic testing contributes to precision medicine. In the general population, breast cancer is caused by multiple factors. About 5 to 10 percent of breast cancer is caused by inherited genetic mutations. The two most important mutations related to breast cancer, BRCA1 and BRCA2, are present in 0.1-0.2 percent of the general population and in a much higher percentage in some minorities. The overall risk to women in the general population of developing cancer by age 70 is 12 percent. However, the average risk is much higher for carriers of BRCA1 (55-65 percent) and BRCA2 (45 percent). While not all women with hereditary risk factors develop breast cancer, the risk for some women may be greater due to other known or unknown factors. Breast cancer is less common in men (0.1 percent), but in men who have the BRCA2 mutation the risk of breast cancer is about 7 percent — 70 times that of noncarriers. In addition to genetic testing of the individual, which provides information about the risk of acquiring the breast cancer, genetic testing of the cancer helps medical professionals establish a prognosis, choose effective therapies and avoid therapies to which the cancer is resistant. In lung cancer today, genetic testing is unfortunately of less benefit, despite much work. Lung cancer is the leading cause of cancer death in men and women, and an external factor, cigarette smoking, is its number 50 | WINTER 2016

one cause — 90 percent of lung cancer is associated with cigarette smoking. However, only 10-15 percent of smokers develop lung cancer in their lifetime, suggesting that there may be a host of differences in susceptibility. A family history of lung cancer doubles the risk of developing lung cancer, but a specific inherited factor has not been identified. Genetic studies of lung cancers continue, not because we want to learn who can smoke risk-free (smoking causes many other cancers and serious diseases) but to find possible genetic drivers of cancer growth that could be targeted by therapy. At present, genetic testing may help guide the therapy in a small fraction of lung cancer cases. The most significant target for the prevention of lung cancer, however, is cessation of smoking, and preventive efforts need not wait for advances in medicine to eliminate 90 percent of lung cancer cases. PROBLEMS WITH PRECISION IN DCS In decompression sickness (DCS), the magnitude and duration of exposure to pressure, the rate of decompression and some external factors determine the outcome of a dive. The role of tissue supersaturation with inert gas is notorious. The deeper and longer the dive and the faster the decompression, the greater the likelihood of supersaturation during ascent and of venous gas emboli (VGE), popularly called bubbles, which may result in DCS. In severe decompression accidents the consequences are generally grave without much variation among individuals due to the overwhelming significance of the external factors. However, in relatively mild dive exposures when the pressure and pressure change are limited, occurrence of VGE is variable but common, while occurrence of DCS is very rare but never zero. The variability in both of these outcomes still escapes our comprehension. After the same dive, some divers may develop a lot of VGE, while others will not develop bubbles at all. In most divers who develop bubbles, the VGE are filtered out by the lungs and cause no harm. In a fraction of divers, however, VGE will pass through the right-toleft shunt from the veins into the arterial circulation, potentially blocking terminal arteries, damaging organs and causing symptoms of DCS. Even when this arterialization of bubbles occurs, few affected divers develop DCS. The only constant is that with more severe dive profiles (greater pressure, longer exposure duration and faster decompression) the average probability of DCS increases. Contemporary dive-computer models measure exposure to an external factor — pressure — over time, but they cannot measure internal factors that modify the saturation and desaturation of the body. These include the amount of blood that perfuses tissues per unit of time, percent and distribution of body fat and other known and unknown factors. Algorithms used in dive computers take into account just the dive profile (the depth, time, breathing gas and rate of pressure change), assume an average body build and metabolic state, and predict the probability of DCS. However, it is clear that the risk is not the same for all individuals, but specific individual factors are not known. Figure 1 shows three stages of individually differentiated risk. STEPHEN FRINK ALERTDIVER.COM | 51

AD 2017 Q1
Q1 2016
Q1 2016
Q1 2016
Q1 2016
AD 2018 Q1
Skycure-Q1-2016-MobileThreatIntelligenceReport
Interim statement Q1/2016
of Fintech Q1 2016
MANAGEMENT REPORT SOPHARMA AD Q1 2012
ADE 2016
Watts On Q1 2016 (For review)