When all Else Fails, Do a History and Physical Examination

A few weeks ago, I was apprised of a 58-year-old gentleman with what appeared to be advanced lung cancer. He was scheduled for a diagnostic CT-guided biopsy and a core of tissue was being submitted to my laboratory. He was considering participating in our assay-directed clinical trial in which we test FDA approved drugs for lung cancer and selects the most active ones for each patient’s therapy. Although we hadn’t met, I knew that he had advanced disease and that he would likely be in need of chemotherapy.

The tissue sample as sometimes happens with core biopsies (as opposed to open surgeries), was too small for a full analysis. We focused only upon the principle platinum-based doublets and a few wells to test the EGFR TKI drugs (erlotinib and gefitinib). Unfortunately, the results did not reveal significant activity for the chemotherapy drugs tested. We did, however, suggest possible targeted therapy approaches. I was concerned that our consultation would consist of the option of experimental drugs or that he go on to a conventional standard drug combination off-study. The final option would be to consider an additional biopsy.

The patient arrived and a careful history and physical revealed that he was a strapping athlete and participant in triathlons — indeed, his symptoms of shortness of breath occurred during a recent 5K. He also said that he had gained weight, which I found surprising. I took the patient into the exam room and conducted a careful physical examination. No sooner did he remove his shirt but I noticed a strikingly protuberant “beer belly.” I was shocked, a tri-athlete? I asked if his feet swelled. He said no, but when I compressed his ankles my fingers left deep impressions. I weighed him, 216 lbs. He had been 199 lbs just two weeks earlier.

Then, I checked his pulse. The problem was I couldn’t really feel it; at least not when he took a breath. It came back only thready with expiration. I checked his blood pressure. He had a systolic pressure of about 88, which fell to undetectable with each inspiration. I looked to his neck and could see the jugular veins prominently distended. I walked with him back to the conference room where his two sons and wife awaited.

I told him that as a medical student at McGill University, the Canadian medical system was not as flush as the American. As such, we were taught the age-old art of physical diagnosis. And I told him that I had just clinically diagnosed cardiac tamponade — the phenomena when fluid, usually malignant, sometimes infectious surrounds the heart and compresses it so severely that it cannot marshal a blood pressure. Left untreated the patient will decompensate and if not attended to, often collapses and dies. To my estimation, he was close. I told him to go directly across the street to the hospital for an immediate x-ray, echocardiogram and fluid aspiration known technically as pericardiocentesis.

I told him not to stop to pay for my consultation; that we could take care of that another time. Upon arrival at the Emergency Department he was in florid tamponade with renal failure, hypotension and an almost unattainable pulse. The cardiac specialist arrived, the patient was taken to the cath lab and two liters of bloody fluid were removed from his pericardial sack. Twelve hours later, I visited this very nice patient in the Critical Care Unit, fluid draining from a catheter in the middle of his chest. He was a different person. Good color, average blood pressure, normal pulse, kidney function almost back to normal.

I shudder to think what might have happened if even a single additional day had passed. Oddly, when I arrived in the cardiac lab that night, the cardiologist congratulated me on the diagnosis and handed me 1.5 liters of fluid from the chest. The next morning, under the microscope, we isolated more cancer cells from his fluid than we could ever need, enabling us to test all the possible drugs and combinations for his treatment.

While I cannot say what the results will show, or whether I will find an active treatment for him, I can say with certainty that diagnostic skills drilled into me by the excellent clinicians at McGill School of Medicine, made it possible for this very pleasant gentleman to live to fight another day.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

2 Responses to When all Else Fails, Do a History and Physical Examination

  1. Gregory D. Pawelski says:

    WOW!

  2. Gregory D. Pawelski says:

    I sent this blog entry to my primary care physician. I wanted to get his response.

    “nicely written. i find it disheartening when i diagnose something and am told that it can’t be correct because the tests do not prove it. i am thinking of a patient recently who had every classic symptom of diverticulitis. it really was textbook. i ordered the CT scan and started medication. the scan that same day came back negative. i saw the patient the next day and he was significantly improved but not 100% (just as he should have been). i saw him the next week and his recovery was right on target. i am still told by the ins. co and a surgeon that he did not have diverticulitis, only diverticulosis (much more benign) because the ct scan did not agree with me. when did we allow the machine over ride the human and not allow for machine error the way we accept human error?”

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