1. Sekeres, Mikkael A. MD, MS

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I just returned from a hematology conference in Nagasaki, Japan, organized by Professor Yasushi Miyazaki. If you're not familiar with him, Professor Miyazaki works in the Department of Hematology and Molecular Medicine Unit at the Atomic Bomb Disease Institute. This institute has tracked survivors of the atomic bomb attack on Nagasaki for decades, monitoring early and late effects from massive radiation exposure. It's the job of his group to monitor hematologic consequences of exposure.

Atomic Bomb... - Click to enlarge in new windowAtomic Bomb
MIKKAEL A. SEKERES, ... - Click to enlarge in new windowMIKKAEL A. SEKERES, MD, MS,

They had a publication in February in the Journal of Clinical Oncology that was absolutely fascinating. In it, they used two databases of atomic bomb survivors totaling more than 86,000 people, looking to see if their rates of developing myelodysplastic syndromes (MDS) were higher than expected.


Now, secondary MDS occurs in about 10% of MDS diagnosed in the US, most commonly from previous exposure to chemotherapy or radiation therapy for other cancers. Rarely, I will see a patient who has a secondary MDS I think is pretty clearly linked to an environmental exposure.


When I say "pretty clearly linked," I'm not talking about a summer working on a golf course, spraying chemicals on the grass. I mean decades of working in a factory with direct radiation or benzene exposure. Declaring that a patient's MDS has resulted from an environmental exposure is tricky business-there are many lawyers who make a comfortable living trying to establish this link in court. It is pretty widely accepted that secondary MDS arises approximately five to seven years following a chemotherapy or radiation exposure, and this is cross-applied to environmental pathogens.


Now, there is no question that rates of some acute and chronic leukemias spiked in Nagasaki following the atomic bomb, for approximately 5-15 years. MDS was not reliably diagnosed in the 1940s and 1950s, though, so detecting a spike in MDS rates occurring 5-15 years following August 9, 1945, would be impossible.


So what Professor Miyazaki and his colleagues did was to start looking for a spike in MDS rates from 1985-2004 among survivors, and compared these rates with expected baseline rates among people of similar age and gender not exposed to the Atomic Bomb.


What they found was that these rates were more than 15 times what you would expect based on current estimated incidence rates. Also, as you might expect, they increased with decreasing distance from the bomb hypocenter and with increasing estimated dose-and they arose 40-60 years after exposure!!


As part of my trip, I was able to tour around Nagasaki, which is a beautiful port city that resembles San Francisco, if San Francisco were humid, had palm trees, and architecture that was less than 60 years old. I went to the Peace Park, the memorial at the hypocenter of the explosion, and to the Atomic Bomb Museum. This museum is devastating in its intensity, in a way that I can liken only to the Holocaust Museums in Berlin or Washington.


It is dark at first, mimicking the darkness that occurred during the fallout, and the first display is of a clock, originally located 1 kilometer from the hypocenter, permanently stuck at 11:02 am, the precise time the bomb exploded. Next you encounter displays on maps showing the extent of destruction, and before and after aerial shots of Nagasaki, showing at first a thriving city, and next a completely flattened wasteland.


Finally, there are the photos of the people-the dead, and perhaps more disturbing, the survivors-bleeding, burned, and maimed, both soon after the explosion, and much later, with keloids and other scars. One section is devoted to long-term effects, with a large image of lymphoblasts and text saying (in both Japanese and English) that rates of leukemia went back to normal by the 1950s. I left the museum with the same empty feeling I did at the Holocaust Museum, wondering how it is possible human beings could do such harm to each other.


Why is this relevant to us in the year 2011? Well, Professor Miyazaki's work has completely redefined how we should be thinking about delays between initial exposures to environmental agents and eventual development of hematologic cancers.


What I saw in that museum transformed this concept from the theoretical to the practical-what these survivors endured, even as children, had to have lasting effects, which became manifest only once they reach their 70s and 80s.


There's another very vocal group in the US who are making claims about late effects, such as MDS, to a defined exposure-the Vietnam Veterans who had contact with agent orange 40-50 years ago.


Agent orange, a defoliant, was sprayed on the jungles of Southeast Asia during the Vietnam War between 1962 and 1971. It was contaminated by 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) during the manufacturing process, a carcinogen. The mixture was frequently combined with hydrocarbons in order to facilitate spraying from aircraft.


If we accept that Professor Miyazaki's research is sound (and I believe it is), then it is possible that Veterans exposed to a carcinogen in their late teens and early 20s could develop a secondary cancer in their 60s and 70s-or, right around now.


We should listen to these Veterans, and devote the same energy and attention to studying these effects and trying to establish a link as has the Nagasaki group with those exposed to the Atomic bomb.