I am currently attending the American Society of Clinical Oncology’s 2008 Gastrointestinal Cancers Symposium in Orlando. Following are reviews of some important new cancer research studies presented during this annual symposium.
A review of data from nearly 500,000 patients with cancers of the colon and rectum confirms what many of us who treat patients from both higher and lower socioeconomic brackets already know: patients with good health insurance tend to present with less advanced cancers than patients who lack comprehensive insurance. In this study, uninsured patients and poor patients covered by Medicaid were twice as likely to present with colorectal cancers that had spread to nearby lymph nodes, and 1.5 times as likely to present with metastatic cancer (i.e., spread of cancer to the liver, lungs or other distant organs), as those patients covered by Medicare or private health insurance plans. This disparity between poor and non-poor patients almost certainly derives from differences in screening between these two populations of patients, as the vast majority of colorectal cancers can be prevented, or at least detected at a very early stage, if everyone were to be screened according to current guidelines. Due to a combination of poor access to screening colonoscopy and other socioeconomic factors, poorer patients often present with very advanced cancers, including colorectal cancers.
As I have stated before, we have a healthcare system, here in the world’s richest country, which is fundamentally broken. The very wealthy can afford both high-quality health insurance and rising healthcare-associated deductible expenses. However, an estimated 47 million people in the United States have no health insurance at all, and many tens of millions more have utterly inadequate coverage. Increasingly, most healthcare experts believe that the implementation of some sort of universal health insurance coverage system is the only realistic solution for our very ill healthcare delivery system.
Another study that was presented evaluated an issue of great relevance to the previous study: the optimal cost-effective approach to colorectal cancer screening. Colonoscopy remains the “gold standard” test for colorectal cancer screening (please review my Archives for additionally discussion of colorectal cancer screening, and current colorectal cancer screening guidelines). On the day before colonoscopy, patients must purge their bowels (which most patients cite as the most noxious aspect of colonoscopy). On the following day, the patient receives intravenous sedation while the physician inserts a long, flexible scope into the rectum. The entire colon and rectum are then examined with this scope, and any abnormal areas thusly identified can be biopsied at the same time. (Rarely, perforation of the colon or significant bleeding can occur during colonoscopy.) However, other methods of colorectal cancer screening have been advocated as well, particularly given the cost and time involved in performing colonoscopy.
Fecal testing for occult bleeding, whether performed alone or in combination with partial colonoscopy, is a quick, cheap and painless test. Performing a partial colonoscopy, by examining only the rectum and lower one-third of the colon (also referred to as “flexible protcosigmoidoscopy”) can also be performed, and reduces the cost and time necessary to evaluate the colon and rectum when compared to complete colonoscopy. Flexible proctosigmoidoscopy does not require the same extent of “bowel prep” as is required for complete colonoscopy, and intravenous sedation is also generally not required for this more limited endoscopic examination. Finally, using a CT scanner to perform “virtual colonoscopy” has been a hot topic of debate, recently, as a potential alternative to conventional “optical colonoscopy.”
A German study enrolled 307 volunteers, and these patients were then subjected to these various colorectal cancer screening tests. In the end, this study found that CT “virtual colonoscopy” was just about as sensitive as conventional colonoscopy in detecting small polyps and tumors of the colon and rectum, while the other methods of screening were considerably less sensitive.
In view of the poor compliance of the general population with screening colonoscopy (considerably less than 50% of eligible patients undergo colonoscopy each year), and in an effort to increase the efficiency and reduce the cost of colorectal cancer screening in our rapidly aging population, some have proposed a greater use of CT virtual colonoscopy. This study, as have other recent studies, appears to show a nearly equivalent level of screening accuracy between current state-of-the-art CT colonoscopy and conventional “optical” colonoscopy. However, there are at least two important potential downsides to CT colonoscopy that must be kept in mind. First, it subjects patients to significant radiation doses at a time when there is increasing evidence that the incidence of certain cancers is probably increased by exposure to such radiation. Secondly, CT colonoscopy is a pure screening test. Unlike conventional “optical” colonoscopy, abnormalities identified in the rectum and colon by CT colonoscopy cannot be biopsied or removed at the time the evaluation is being conducted. Indeed, any polyps or tumors that are identified by CT colonoscopy must then be reassessed by conventional colonoscopy, at which time they can be removed or biopsied. Because of these fundamental shortcomings associated with CT virtual colonoscopy, my recommendation to patients is that they undergo conventional “optical” colonoscopy if they meet the current guidelines for such screening, and if they are healthy enough to tolerate the bowel purge and intravenous sedation necessary to perform this screening test (of note, current CT colonoscopy examinations require the same unpleasant purging of the bowels as with conventional colonoscopy and patients do not receive any sedation while air and a barium-like material are pumped into their rectum during CT colonoscopy…).
Somehow, our society must find a way to cover the very significant costs associated with screening colonoscopy in order to prevent the far more costly and tragic diagnosis of advanced cancers of the colon and rectum.
Cancers of the esophagus are generally pretty bad actors, as cancers go. In the majority of cases, these aggressive tumors are already quite advanced by the time they cause enough symptoms to compel patients to seek medical evaluation. Unlike most other cancers, the incidence of esophageal cancer appears to be rising dramatically in the United States, and particularly cancers of the lower esophagus in white men (there is a great deal of debate about why this is happening, although the concomitant rise in the levels of obesity and gastroesophageal reflux disorder, or GERD, in our population are the two most commonly cited potential risk factors, as recently reviewed by me [please review my recent Archives]).
A new study from Ireland adds further data to support concerns that rising obesity levels, and obesity-related abnormalities in metabolism, may play a causal role in the development of lower esophageal cancer. A premalignant condition of the esophagus, known as Barrett’s esophagus, or intestinal metaplasia, is a known precursor of lower esophageal cancer. In this Irish study, the patients with a type of Barrett’s esophagus associated with the highest risk of progression to esophageal cancer were also found to have the highest levels of central obesity (i.e., increased fat distribution of the lower abdomen and hips), and were also more likely to have obesity-related abnormalities of metabolism, commonly referred to as the “metabolic syndrome” (this syndrome is associated with increased blood levels of “bad cholesterol” and other inflammatory substances, early signs of diabetes, and other metabolic abnormalities, and this syndrome has previously been linked to an increased risk of diabetes, stroke, and heart attack).
The results of this Irish study adds to a growing body of research implicating obesity, and central obesity in particular (which is more common in obese men than in obese women, by the way), to a variety of serious health problems, including various cancers, and possibly to lower esophageal cancer, specifically.
Unfortunately, pancreatic cancer remains a truly formidable disease, and one of the most lethal of all cancers The overall cure rate for this terrible disease has not really budged much at all in recent decades, as the biological behavior of pancreatic cancer is especially aggressive, and as most patients initially present with advanced disease. It is estimated that only about 15-20% of patients diagnosed with this disease will even be eligible for surgical resection, which is the primary treatment for this cancer. Although very modest improvements in survival have been achieved by adding chemotherapy (and, particularly, with a chemotherapy drug called gemcitabine) and radiation therapy to surgery, pancreatic cancer remains essentially resistant to almost all forms of therapy. Sadly, only about 10-15% of patients with the most common form of pancreatic cancer can be cured of their disease with currently available therapies. Because of the high lethality of pancreatic cancer, and its resistance to most forms of treatment, a great deal of research is being directed at trying to understand the biology of this disease better, in an effort to develop more effective therapies.
Several presentations at this symposium provided tantalizing insights into some of the biological pathways that pancreatic cancer cells might be using to survive chemotherapy and radiation therapy. One study looked at the role of a protein, beta-catenin, that pancreatic cancer cells appear to use to resist the effects of radiation treatment. When the researchers blocked beta-catenin function in pancreatic cancer cells in the lab, they were able to convert these normally radiation-resistant cancer cells into radiation-sensitive cells. The next step in this research, of course, is to develop therapies that can block beta-catenin activity in the pancreatic tumors of humans, and to study such treatments in appropriate clinical research trials.
The increasing clinical importance of so-called “molecular medicine” was illustrated by another presentation that evaluated naturally-occurring genetic variations in genes that are associated with the uptake and metabolism of gemcitabine into pancreatic cancer cells (this genetic variability, often referred to by the abbreviation “SNPs,” for single nucleotide polymorphisms, is easily observable by looking at other people around you, as they are responsible for the normal variations in the color of our eyes and hair, among other traits).
Although several clinical studies have shown modest but favorable activity by gemcitabine against pancreatic cancer (especially when combined with radiation treatments), other studies have found minimal—if any—clinically significant benefit from this chemotherapy drug. A new study, presented at the ASCO Gastrointestinal Cancers Symposium, may shed some light on these prior contradictory research results. The researchers specifically studied 8 different genes associated with gemcitabine uptake and metabolism by sequencing these genes in the blood cells of 126 patients with pancreatic cancer. The results of this study showed that patients with the most favorable variations in these genes, in terms of pumping gemcitabine into cells and in preventing rapid metabolism of the drug, had a much better survival following treatment with gemcitabine and radiation therapy after surgical resection of their cancers than did those patients with unfavorable “SNPs” in these same genes. A very interesting associated observation was that those patients who had some of the worst gemcitabine-related toxic side effects not only tended to have very specific genetic variants in several of the evaluated genes, but these same patients also tended to have the best survival as well. This observation adds further evidence that naturally occurring variations in genes involved in the uptake and metabolism of specific chemotherapy drugs may have a significant impact on patients’ responses to those drugs. Findings such as these give hope to those of us who believe that, one day, the treatment of patients with cancer will become a highly individualized undertaking, based upon—and optimized for—the specific genetic make-up of each patient’s unique tumor.
Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity.
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center
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Copyright 2008. Robert A. Wascher, MD, FACS. All rights reserved.
Dr. Wascher's Archives:1-20-2008: Testosterone Levels & Risk of Fractures in Elderly Men; Air Pollution & DNA Damage in Sperm; Statins & Trauma Survival in the Elderly
12-16-2007: Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality