Modern genotyping techniques offer an alternative to classical staging. In the latest issue of The New England Journal of Medicine (356(1), January 4, 2007), a group of researchers from Taiwan report on a using gene signatures for determining clinical outcome in non-small cell lung cancer (NSCLC) (Chen, HY et al.: A five-gene signature and clinical outcome in non-small cell lung cancer).

The Taiwan group used microarrays to look at some 672 genes that were associated with invasive activity. They fine-tuned their analysis to identify 16 genes that were associated with survival and further reduced the set to five genes that were “independent predictor[s] of relapse-free and overall survival.” The researchers note that using PCR techniques with a small set of genes can be a practical clinical test.

For example, the authors note that “cisplatin-based adjuvant chemotherapy is effective in some patients with NSCLC. We propose that patients who have tumors with a high-risk gene signature could benefit from this type of adjuvant therapy, whereas those with a low-risk gene signature may be spared what would be unnecessary treatment.” The side-effects of cis-platin, as many of you know, can be quite unpleasant.

I’ll admit the actual article—especially the methods section—was rough sledding. Much of the vocabulary of modern genetic medicine is foreign to us who were in med school 25 or more years ago. But the fact remains that genetic medicine is becoming an ever greater part of modern medical practice, and it behooves us all to become familiar with its principles.

I’ve posted on this general topic elsewhere in the blog, including here and here.

Technorati Tags: cancer staging, non-small cell lung cancer, microarrays, gene signatures

It’s been ninety-four days since I had coronary artery bypass surgery.  I feel fine.  Truly, the only reminders of the surgery are an impressive scar down the middle of my chest and somewhat shorter chest hair.  I’ve also started back to part-time work as a doctor.

I was worried when I started back that I might be a bit rusty.  Fortunately, that hasn’t been the case. But there’s one thing I forgot during my six-month break from practicing clinical medicine (I retired from my medical group at the end of May)—I’d forgot just how much uncertainty is involved in the practice of medicine.

In a general medical practice, most of the patients we see have well-defined problems, such as high blood pressure, carpal tunnel syndrome, shingles, backaches, and the common colds of either medicine (a virus) or psychiatry (depression).  But in the mix of cases there are also a number that defy classification either because the diagnosis is unclear or because the treatment involves too many variables.

Case in point: the 73 year-old woman I’ve just seen for a “cough”.  Her chest xray shows a tiny bit of fluid in her lungs and her history and physical examination suggest that she may have a mild case of congestive heart failure.  But she also had a mastectomy for breast cancer ten years ago, and recurrent breast cancer can also spread to the lungs, causing fluid to collect and producing a cough.

And while I’m pondering how to proceed with that case I see another patient, a young man whose complaint is that he feels “lousy” and has a headache  And, indeed, he has a low grade fever and a fast pulse.  Most likely he has some sort of infection.  But what?  And where?   I check his blood count.  He has an elevated white blood cell count, further evidence of an infection.

In general, this young man doesn’t look bad.  There’s no evidence that the headache represents a problem with his brain.  He drove to the clinic on his own; he’s able to eat and drink; and he has a comfortable home within a few miles of the clinic. So I decide to send him home with a diagnosis of “viral syndrome” and advise him to rest, drink some herbal tea, and take Tylenol for his fever.  I also know full well that he could have something else and something much worse.  These kind of vague symptoms could be harbingers of endocarditis or encephalitis or even some sort of smoldering tumor.  I have been fooled before.  But I have to trust my intuition here.

So both patients go home.  The woman with the cough is started on a diuretic for presumptive congestive hear failure and pulmonary edema.  I will see her in a few days to repeat the chest xray and see how she feels.  If the diuretic has done nothing and the fluid continues to collect I will tap her chest and examine the fluid.

The young man goes home with the admonition to come back ASAP if he feels he’s getting worse.

When I was a resident, one of my wise professors told me that to practice medicine one is often forced to act on insufficient information.  He also told me that in a busy clinic day– with dozens of back-to-back 15-minute appointments—doctors have to move fast.  It’s the combination of speed and uncertainty that I believe contributes most to the stress of practicing medicine.

And, not to keep you hanging, the woman with the fluid in her lung responded to the diuretic: the fluid decreased and the cough stopped.  The young man who felt lousy never did return to the clinic so after a week I phoned his home to learn that he and his girlfriend were “up at Tahoe on a ski trip.”

Technorati Tags: general medicine, family practice, uncertainty

At the time I arrived, the HIV epidemic was raging. In Rockford, most of the victims were iv drug users, their partners, and their children. HIV wasn’t really a gay thing in Rockford because when a gay Rockfordian was old enough to leave town, he did—usually for Chicago.

Faced with the epidemic, I asked my Rockford colleagues why no one had started a needle exchange program. “Oh,” I was told, “we can’t do that here. Rockford is a conservative town…”

But I digress.

Rockford is in the medical news big time this week because of a study just published in the December 15 issue of The New England Journal of Medicine . The study looked at colonoscopies performed by twelve gastroenterologists practicing in Rockford. The main conclusion of the study was that the longer the gastroenterologist took to do the colonoscopy, the more likely he was to find an advanced neoplasm—a polyp that showed precancerous changes.

The immediate result of this will be for every gastroenterologist who performs colonoscopies to slow down! Colonoscopy is considered the gold standard of screening tests for colorectal cancer. Colonoscopy is more likely to find a neoplasm than simple sigmoidoscopy, which only looks at part of the colon. Colonoscopy is also considered more sensitive for finding early neoplasms than is fecal occult blood testing. And in recent years, both “virtual colonoscopies” (colonoscopy by helical CT scanning) and tumor DNA screening of stool have been proposed as alternatives.

The DNA screening test is apparently very sensitive—88%–for all stages of colorectal cancer and is entirely non-invasive. Results of a trial of the test will be published in the January 2007 issue of Clinical Gastroenterology and Hepatology.

To return to Rockford, I want to add that I was treated very well during my time there. The local medical community was welcoming and helpful. I had many opportunities to stay on in Rockford. But I’m a California kid.

Technorati Tags: colon cancer, colon cancer screening, colonoscopy, New England Journal of Medicine, Rockford IL, HIV, DNA test for colon cancer screening

Absolute pitch is the same as perfect pitch, and there us some good preliminary evidence that this trait runs in families an likely has at least a partial genetic basis. The Absolute Pitch Study’s Web site seeks to recruit subjects. The site includes an auditory test—you can hear the tones through your computer’s sound card.

Alas, I don’t have perfect pitch, but I do have one of those nifty little electronic tuners that clips onto the peghead of my guitar!

Technorati Tags: music, perfect pitch, genetics of music, university of California, San Francisco

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