Posts Tagged ‘colon cancer’

Cancer screening Part 2: what works?

Sunday, August 11th, 2013

A blog post in The New York Times online recently addressed this issue noting, "Definition of Cancer Should Be Tightened, Scientists Say."

Here's a typical scenario: We've had a screening test for some form of the illness many of us fear the most (actually, I fear Alzheimer Disease at least as much). Then we hear the words, the really scary ones. "You've got cancer." We may not hear the modifiers that come before the C word, or anything else that follows. The National Cancer Institute's (NCI) working group wants to clarify that some conditions are pre-malignant (they're not cancer yet and, in certain cases, may never become carcinomas {another term for cancer}).

I want to return to the JAMA preprint article  I mentioned in my last post; it's titled "Overdiagnosis and Overtreatment in Cancer? An Opportunity for Improvement"

The group focused on cancer screening to include breast, lung, thyroid, colon, cervix, melanoma and prostate exams.  They tracked the incidence of a variety of cancers over the thirty-five-year period from 1975 to 2010 and found three different result patterns have been noted as more and more of us are screened for more and more conditions.

Some cancers have been diagnosed somewhat more frequently, but in many cases are less serious variants, less likely to kill us, so, overall, they are causing fewer deaths. Other malignancies are being found less frequently (due to improved and/or more frequent screening resulting in precancerous stages being treated) and the death rate from them has gone down considerably. And some cancers are being diagnosed much more often, but much of that increment is what the researchers termed "indolent disease," less active or progressive disease and overall their death rate is nearly unchanged or increased much less than the percentage change of their being diagnosed would indicate.

Let's take cancer of the prostate for an example of the first group. The incidence (rate of occurrence) in cases per 100,000 men has gone from 94 to 145.12, a fifty-four percent increase, while the death rate from the disease has gone down 30%.

So we're doing better with treating this form of cancer, seeing a lower mortality rate, but we're discovering considerably more cases that are not causing deaths. As I said in my last post, I've decided not to have any more PSA tests; at my age (72), other things are much more likely to kill me than prostate cancer. I clearly would have made the opposite choice (and did) at age 45 or 55.

Mammograms can save lives; they also can find pre-malignant lesions.

Mammograms can save lives; they also can find pre-malignant lesions.

The other tumor in the first group is breast cancer. Mammography has certainly become more of a routine procedure looking for breast lumps, but while the incidence of breast lesions has gone up 20% in the thirty-five year interval the NCI group looked at, the death rate has fallen by 30%. Much of that is due to what is termed adjuvant therapy, e.g., chemotherapy following surgery.

But another group of women with a positive mammogram have a less serious form of disease called ductal carcinoma in situ. The NCI webpage on this tumor says it is noninvasive, but some (uncertain) percentage of these can progress to an invasive form.

What is DCIS? It's the most common type of non-invasive breast cancer, starts in the milk Ducts, has been termed a Carcinoma and is In Situ which means "in its original place."

The NCI group who published the JAMA article terms it a premalignant condition and would prefer it not be called a carcinoma. Most of these lesions are small (~70% are less than 1 cm in size) and 80% are not found by breast examination, but show up on a mammogram.

Another NCI group, however, reviewed the medical literature on DCIS saying until recently the usual response to its discovery was a mastectomy. More recently there have been two randomized, controlled trials of breast-conserving surgery (lumpectomy) combined with radiation therapy and even more recently a double-blind prospective trial utilizing chemotherapy with the drug tamoxifen given daily for 5 years in addition to lumpectomy and radiation.

A control group had the surgery and radiation plus a placebo. The group that got tamoxifen did considerably better and other clinical trials are in progress.

The second group of tumors included colon cancer and cervical cancer. The statistics are fascinating. For colon cancer the incidence rate has gone down 31% and the death rate 45% and the trend is quite similar for cancer of the cervix (5 and 59% decrements)

We all have a colon, so let me focus on that cancer for a moment with a recent personal vignette.

My father had a large sessile polyp, a projecting growth without a stalk, in the very first part of his colon. It was initially benign, would have been difficult to remove and he was in his late 70s. so it was repeatedly observed and biopsied. Eventually it had a superficial layer that was cancerous. By then he was nearly ninety and the decision was to shave off layers until what was left was benign.

So that gives me a positive family history of colon cancer.

My previous colonoscopy (2006) was totally negative and without that family history my gastroenterologist would have said, "Come back in ten years."

Some colon polyps are relatively easy to remove.

Some colon polyps are relatively easy to remove.

Because of Dad's polyp, my GI doc wanted me back in seven years. And he was right; this time I had three small polyps, all of them benign and all on stalks (The technical term is pedunculated.), making them easy to snip off. I had decided to stay awake and watch and the procedure, while somewhat uncomfortable, was fascinating. I went home reasonably confident that my polyps were benign.

But there are three kinds of those colon polyps, according to the followup letter I received. Type one is of "minimal clinical significance." Type two, which I had, is benign, but potentially precancerous. Early colon cancer screening for first-degree relatives is recommended. It was suggested I speak to parent (both dead), siblings (my only sib died at fifty-seven) and children (my daughter), so they can discuss colon cancer screening with their physician.

I copied the letter to bring to my daughter on a vacation trip we're taking.

Type three is also benign, but there's considerably more chance of it turning into a cancer.

So my next colonoscopy will be in five years this time.

If I had a totally normal colon at age 72, my GI doc had said he'd not suggest any more colonoscopies ever. My routine ten-year-interval next one would have been at age eighty-two and that, he felt, is too old to screen someone whose seventy-two-year-old colon was negative for any polyps.

But with their natural history of being potentially precancerous, the discovery of types two or three leads to a change in schedule and a family search is quite reasonable.

And, I take it, that's why the incidence of colon cancer and the death rate from that malignancy have gone down over that thirty-five-year period. There's presumably been better treatments developed for those who do end up with that form of cancer, but by dong colonoscopies and removing pre-cancerous lesions (i.e., polyps), we're preventing many of them from altering into malignant tumors.

So those are examples of the group of tumors that are being discovered more often, but are causing fewer deaths and of one (colon cancer) that our screening is helping prevent.

I'll write about cancer of the cervix and of thyroid cancer and melanomas next time.




Should I be taking aspirin?

Wednesday, January 30th, 2013

I take a dose equivalent to 1/4 tablet of aspirin

One of our friends recently told my wife she'd stopped taking aspirin after a news report linked regular use of the medication to macular degeneration. We've both taken 81 mg of aspirin a day and, after I'd heard that people may not absorb the enteric coated form well (and I couldn't find any other form in that size at the local drugstore), I'd ordered ten bottles of chewable orange-flavored aspirin online from Amazon.

Then I decided to read the medical reports that our friend's recommendation had been based on. She doesn't have a medical background and hadn't looked at the original data, but instead had seen a warning in a newspaper article. Let's start at The New York Times blog. On Dec 12, 2012 they published an article by Anahad O'Conner titled "Aspirin Tied To Rare Eye Disorder."

It's a very well-worded article written by a 31-year-old, Yale-educated Times reporter who writes a weekly science column and has published two books He notes the article he based his piece on was from JAMA with the lead author, Dr. Barbara Klein, being a professor of ophthalmology at the University of Wisconsin, Madison. Since I'm a UW graduate (BS 1963, MD 1966), I was particularly interested in her study.

It used data from the Beaver Dam Eye Study, started in 1988-1990 and concluded in 2010. O'Connor very appropriately noted this was an observational study, not a prospective, controlled research project. In other words a group of ~5,000, aged 43 to 84, agreed to have regular eye exams and reports were published after the 5-, 10-, 15- and 20-year followups.More than 300 publications have resulted from this project with data supporting a relationship of cataracts and age-related macular degeneration (AMD) to cigarette smoking.

Klein's paper stated that an estimated 19.3% of US adults take aspirin on a regular basis. It's commonly recommended for anyone who has had a heart attack (secondary prevention), but many   of us who've never had evidence of coronary vascular disease also take aspirin. This is primary prevention and is controversial with some data suggesting reduction of heart attacks in men over 45, but not women, although they may have a 17% reduction in stroke incidence.

A senior who has AMD may need a magnifying glass.

A January 21,2013 article from an Australian group reported a two-fold increase in AMD of a particular type, independent of smoking habits. Nearly a quarter of regular long-term aspirin users developed neovascular AMD, two and a half times the percentage of those who did not regularly take aspirin.

A 2001 paper in the Archives of Ophthalmology reported a randomized, double-masked, placebo-controlled study of low dose aspirin (one adult tablet every other day) plus 50 milligrams of beta carotene (a vitamin A precursor rated possibly effective in treating advanced AMD) among over 20,000 US male physicians aged 30 to 84 in 1982. The study was stopped after ~5 years due to a statistically extreme reduction (44%) in first heart attacks. There were fewer cases of AMD in those taking low-dose aspirin than in those who got the placebo.

There's also some data supporting aspirin's role in cancer prevention, especially in malignancies of the colon. Here the benefit was unrelated to aspirin dose (75 mg/day and up), but increased with age.

So let me look at my own risks: my dad had a large polyp in the earliest part of the colon, an area hard to see even on colonoscopy. It was initially felt to be benign, but later had some areas of low-grade malignancy. He also had macular degeneration in his remaining eye  diagnosed at age 90+ (the other eye having been removed nearly sixty years previously after a bad cut and a subsequent infection). My brother died of a heart attack at age 57 and my mother had a heart attack at age 74 with a cardiac arrest; (Dad resuscitated her and she lived to age 90).

The editorial that accompanied the recent JAMA article is thoughtful and impressive. Its title was "Relationship of Aspirin Use With Age-Related Macular Degeneration: Association or Causation?" and it concludes "From a purely science-of-medicine perspective, the strength of evidence is not sufficiently robust to be clinically directive." It then switches to a different viewpoint, the art-of-medicine perspective, saying maintaining the status quo is currently the most prudent approach, especially in secondary prevention (someone who has already had a cardiovascular event). For those of us who haven't, the risks versus benefits should be individualized based on our own medical history and value judgement.

I'm going to discuss this with my own physician but not stop taking a chewable 81 mg aspirin daily until I do.

An Herbal Medicine that may help colon cancer patents

Wednesday, April 4th, 2012

Can herbal mixtures augment the effects of traditional therapy?

I've been skeptical about many of the claims made for herbal medicines, as they're often based on case reports or other empirical data and seldom seen to meet the rigorous standards I'm used to for new medical findings. Yet millions of people over the last four thousand years have used Oriental medicine mixtures and some of those are now being subjected to intense study.

The NIH's National Center for Complementary and Alternative Medicine has a website that provides useful links into this complex and sometimes baffling field. A 2007 survey showed 38% of Americans use CAM, often in the form of dietary supplements, where well-designed clinical trials may be lacking and the safety and effectiveness of the CAM therapy is unclear.

I want to focus on one of these CAM therapies that has been examined in detail and looks exceedingly promising...thus far.

The research of Yung-Chi Cheng, the Henry Bronson Professor of Pharmacology at the Yale School of Medicine, was highlighted in The Wall Street Journal in an article titled, "Chinese Medicine Goes Under the Microscope." He was raised in Taiwan, but his PhD is from Brown University. Now he directs Yale's Therapeutics/Chemotherapy Program and has published ground-breaking work in major research journals.

Dr.Cheng has been studying a traditional Chinese medicine for 12 years. Many of China's 75,000 therapeutic concoctions may seem strange to us, consist of various combinations of 5,000 different plants and have never been tested for efficacy in a fashion we would expect. On the other hand many of our accepted medicines originally came from botanical products. Professor Cheng decided to bridge the gap, studying one particular ancient herbal drug using modern Western methods. Initially he was met with skepticism; his colleagues were concerned that he'd find a lack of consistency in the herbal preparation. Since then Yale sponsored a biotechnology company to ensure uniformity in the plants used to produce the herbal mixture known in the Orient as huang qin tang. Here, as PHY906, it is used with traditional chemotherapy to reduce side effects.

This is a mixture of four different herbs, the flowers of the Chinese skullcap plant, the fruit of the Chinese date tree, Chinese Licorice and Chinese peonies. It's a complex melange, with 62 active chemicals that apparently must be used together, a form of polypharmacy (several drugs being given at the same time). Thus far animal experiments, reported in two scientific journals, BMC Medical Genomics and Scientific Translational Medicine have been very promising ( a conclusion in the former notes it can decrease toxicity in normal cells while promoting tumor cell death) and human Phase II studies are beginning (Phase I clinical trials are small studies looking at safety, Phase II examine efficacy, does the new drug do what its supposed to; Phase III are considerably larger and compare a drug  to existing or standard treatments).

In 2003 Professor Cheng went on to establish the Consortium for Globalization of Chinese Medicine which he now chairs. Aims of the international group include using modern methods to ensure quality control of herbals and coordinating clinical trials in disparate areas of the world.

The target is colon cancer

His work was published online in the journal Nature in a 2010 article, "How an 1,800-year-old herbal mix heals the gut." In 2011 he received a $6.7M grant from the National Cancer Institute for his project titled, "Chinese Herbal Medicine as a Novel Paradigm for Cancer Chemotherapy."

I await his study results eagerly.