Transition…

I am currently transitioning, both geographically and professionally, as I write this column.  I have tremendously enjoyed three wonderful years as a research surgeon & oncology fellow at the John Wayne Cancer Institute in Santa Monica, CA.  Having completed my three-year fellowship there on June 30^th, I will now be leaving my native Southern California to take a new position as Chief of Surgical Oncology, and Director of Oncology Research, at a major teaching medical center in Honolulu.  I will also be taking about 3 months away from patient care, research and teaching activities to finish two books that I have fallen behind in completing.  During the next three months, I will continue to write this column, although perhaps not on the same weekly basis as has been the case for the past two years. 

Stay tuned for more cutting edge clinical research results, Dear Readers.

Colorectal cancer is the second most common type of cancer in the United States.  More than 140,000 people will receive this diagnosis in 2003, and more than 60,000 Americans will die of the disease this year.  The appropriate interval between colon screening exams has been debated for many years.  Currently, the American Cancer Society recommends, beginning at age 50, a yearly stool blood test (“fecal occult blood test”) and flexible sigmoidoscopy every 5 years.  Moreover, every 5-10 years, the flexible sigmoidoscopy should be combined with an air-contrast barium enema.  An alternative to the barium enema-plus-sigmoidoscopy option is to undergo complete colonoscopy every 5-10 years.  It should be stressed that recent studies have shown colonoscopy to be more accurate than sigmoidoscopy-plus-barium enema.  Unlike barium enema studies, colonoscopy also allows for the biopsy or removal of polyps and other small tumors found at the time of colorectal screening.

These colorectal cancer recommendations change every few years, although often without a great deal of underlying scientific evidence.  An interesting new study in the Journal of the American Medical Association looked at the results of repeat sigmoidoscopy 3 years after a previous negative sigmoidoscopy in 9,317 volunteers enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).  This average age of volunteers in this randomized prospective study was 65.7 years, and 61.6% were men.

At repeat sigmoidoscopy, 1,292 (14%) of the patients were found to have a colorectal polyp or mass, despite having undergone a negative sigmoidoscopy 3 years previously.  Of these 1,292 patients with new findings of a colorectal mass, 292 (3%) were found to have precancerous adenomas or cancers in their lower colon or rectum (6 cancers were found).  When the study’s authors compared the results of the initial and subsequent sigmoidoscopies, they determined that 81% of patients with advanced precancerous adenomatous polyps had been adequately examined during the initial sigmoidoscopy. The study concluded that repeat sigmoidoscopy 3 years after a negative sigmoidoscopy still detects a considerable number of precancerous polyps, as well as a smaller number of actual colorectal cancers.  Although some polyps may arise within a period of 3 years, most of the polyps and cancers that were discovered during the second sigmoidoscopy exam were most likely missed during the initial exam.

It is important to understand that this study looked at only partial endoscopic examination of the colon and rectum, and did not assess the full length of the colon.  Flexible sigmoidoscopy is capable of evaluating only the lower one-third to one-half of the colon.  In order to evaluate the entire colon, one has to perform a colonoscopy (the most accurate method of colorectal screening) or flexible sigmoidoscopy plus air-contrast barium enema.  Thus, I find the implications of this study even more concerning, as the compliance rate for complete colorectal screening is very low in the United States (fewer than 10% of people over age 50 are in full compliance with the current colorectal screening recommendations).  It seems clear from this study that additional large-scale studies of full colonoscopy are merited.  The optimal cost-to-benefit ratio of routine colonoscopic examinations remains unclear at this time, and there is precious little research data to support current screening recommendations.  Additional studies should therefore address these concerns, as well the critical issue of poor patient compliance.

Walking, Diabetes & Death

Over the past year, I have reported on several studies that have confirmed a significant health benefit with even relatively modest levels of regular exercise.  The current issue of the Archives of Internal Medicine contains a study of 2,896 adults with diabetes who participated in the 1990-1991 prospective National Health Interview Survey.  These study participants were followed for an average of 8 years after completing an intensive health and lifestyle survey.  The study found that, when compared with inactive individuals, those who walked at lest 2 hours per week had a 39% lower risk of dying from any cause.  Death due to cardiovascular causes, specifically, was reduced by 34%.  The study also took into consideration a number of potentially significant co-existing risk factors prior to calculating the impact of walking in mortality levels, including sex, age, race, diabetes duration, physical limitations, body mass index, smoking, and other health-related risk factors.  Among diabetic adults who walked 3-4 hours per week, death due to all causes was reduced a rather remarkable 44%, while death due specifically to cardiovascular disease was reduced by 43%.  The study concluded that for every 61 diabetic adults, one death per year could have been avoided if they could have been persuaded to walk only 2-3 hours per week!

This study is additive to many others that demonstrate clear-cut and significant reductions in the risk of dying prematurely with even modest regular physical activity.  At the same time, these studies are really showing us how little regular physical activity we, as a nation, indulge in these days, as well as the enormous health costs of such inactivity….

Green Tea Extract & Cholesterol

There are many advocates of the purported health benefits if green tea.  Some studies appear to show at least a weakly positive correlation between drinking green tea and lower rates of cardiovascular disease, and of some cancers.  Unfortunately, other similar studies do not appear to confirm such benefits.  However, green tea is known to be rich in compounds with antioxidant activity, including isoflavones.  One such green tea isoflavone, theaflavin, has also been experimentally linked to a reduction in total cholesterol levels, and in the so-called “bad cholesterol” (LDL) in particular.  However, recent studies looking at green tea consumption have failed to show any significant LDL reductions.

A new study in the current issue of the Archives of Internal Medicine looks at the effects of theaflavin-enriched green tea extract on the cholesterol levels of adults with mildly-to-moderate high cholesterol levels.  A total of 240 Chinese adults enrolled in this randomized placebo-controlled study.  All study participants were placed on a low fat diet, and were randomized to receive either theaflavin-enriched green tea capsules (375 mg) or placebo capsules for a period of 12 weeks.  After 12 weeks, the folks who received the green tea extract experienced an 11% reduction in overall cholesterol levels, and a 16% reduction in LDL levels.  Triglyceride levels also declined by about 3% in the group of patients taking the green tea capsules.  No adverse health effects were noted among the group of volunteers assigned to take the green tea extract capsules.  In contrast, there were no significant changes in the blood levels of total cholesterol, LDL or triglycerides among the patients receiving placebo capsules.

This is an interesting study, and appears to rather convincingly demonstrate the clinical utility of enriched green tea extract for the management of mild-to-moderate hypercholesterolemia.  Not only did enriched green tea extract appear to moderately reduce total cholesterol and LDL levels, but it did so without any noticeable adverse health effects.  (Note: If you have elevated cholesterol or LDL levels, please check with your doctor before making any changes in your dietary or mediation regimens.)

Briefly…

Archives of Internal Medicine:  A review of medication errors in a large medical center between 1995 and 2000 was conducted.  Pharmacists intervened 14,983 times during the study period, and 4,768 of these interventions were for medication errors (24 medication errors per 100 patient admissions).  The most common error involved patients receiving the wrong medication (36% of errors) or the wrong dosage (35% of errors).  Not surprisingly, prescribing physicians were responsible for most of the errors, and the transition from outpatient to inpatient status was the most common interval for medication errors.  Higher levels of medication errors also occurred during the annual summer turnover of interns and residents (a well-known phenomenon).  The identification of these factors associated with medication errors should aid in finding solutions for this potentially serious problem.

New England Journal of Medicine:  Until recently, patients with advanced breast cancer were often advised to undergo high-dose chemotherapy.  This chemotherapy regimen is so toxic that it essentially destroys the bone marrow stem cells that give rise to the blood’s red and white cells.  So, patients who receive high-dose chemotherapy invariably require post-chemotherapy transfusion of stem cells (either their own, or somebody else’s stem cells) following chemotherapy.   Unfortunately, most of the scientific data supporting high-dose chemotherapy resulted from research performed in South Africa almost a decade ago, the results of which were subsequently found to have been largely fabricated.  Not surprisingly, over the past decade, high-dose chemotherapy for breast cancer has fallen out of favor in the United States, and in most parts of the world.  However, there are still proponents of this therapy here and there.  Two studies in this journal have taken another look at this form of therapy for high-risk breast cancer patients (generally defined as patients with 4 or more positive lymph nodes, large breast tumors, or spread of tumor cells outside of the breast or lymph nodes).  The first study found a modest 17% relative improvement in relapse-free survival among patients with positive lymph nodes following high-dose chemotherapy and autologous stem cell transplantation (65% survival at 57 months average follow-up, versus 59% survival for conventional chemotherapy). 

The second study, however, found only a mild improvement in time to cancer relapse, but no significant improvement in survival.  The findings of this second study essentially mirror the results of other large studies over the 5-8 years.

Unfortunately, it appears premature to seriously consider high-dose chemotherapy and stem cell transplant for most patients with breast cancer at this time.

Dr. Robert A. Wascher