Health Report:

Vitamin D & Colorectal Cancer Survival

“A critical weekly review of important new research findings for health-conscious readers…”

Updated:  09/20/2009

The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author.  Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.

VITAMIN D & COLORECTAL CANCER SURVIVAL

The authors of this clinical research study analyzed volunteers within the massive Nurses’ Health Study. A total of 1,107 volunteers were diagnosed with colon or rectal cancer, between 1986 and 2004, after joining this long-term prospective public health study. Using a previously validated scoring system that accurately predicts Vitamin D levels in the blood, the researchers assessed the survival rates of these colorectal cancer patients as a function of their Vitamin D scores. (It is important to note that Vitamin D scores were calculated prior to the diagnosis of colorectal cancer in these patient volunteers.) The results were rather profound.

The Vitamin D scores for these 1,017 colorectal cancer patients were broken up into a five different ranges, and the patients with the highest Vitamin D scores were then compared with those in the lowest “quintile” with respect to cancer-related mortality and overall mortality. This analysis revealed that patients with the highest Vitamin D scores were 50 percent less likely to die of colorectal cancer during the course of this study, and 38 percent less likely to die from all causes, when compared to the patients with the lowest Vitamin D scores.

While the exact mechanisms whereby Vitamin D and calcium may decrease the risk of colorectal cancer, and the risk of death following a diagnosis of colorectal cancer, are still being studied, there is already intriguing data showing that Vitamin D supplementation can “up-regulate” the activity of genes in both premalignant and malignant colon and rectal tumors that, in turn, increase the death rate of the abnormal cells that make up such tumors (through a pathway known as apoptosis).

While no nutrient or medication has been shown to prevent all colorectal cancers, or to cure all colon and rectal cancers once they develop, there is an increasing amount of high-quality clinical data suggesting that higher levels of Vitamin D in the blood are associated with a decreased risk of both premalignant and malignant colon and rectal tumors. Now, based upon this new study’s results, it appears that higher Vitamin D levels may also be associated with improved survival following the diagnosis of colorectal cancer as well. The impact of Vitamin D levels on colorectal cancer survival also mirror similar findings that I have recently reported on with respect to breast cancer (Breast Cancer Recurrence, Death & Vitamin D).

Look for a much more detailed discussion of the role of Vitamin D, and other dietary and nutritional factors, in cancer prevention in my forthcoming book, “A Cancer Prevention Guide for the Human Race.”

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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

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Dr. Wascher is an oncologic surgeon, a professor of surgery, a widely published author, and a Surgical Oncologist at the Kaiser Permanente healthcare system in Orange County, California

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(Anticipated Publication Date:  March 2010)

(Click above image for TV36 interview of Dr. Wascher)

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Send your feedback to Dr. Wascher at:

rwascher@doctorwascher.net

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Dr. Wascher’s Biography

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Links to Other Health & Wellness Sites

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http://doctorwascher.com

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Copyright 2007 – 2009

Robert A. Wascher, MD, FACS

All rights reserved

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Dr. Wascher’s Archives:

9-13-2009: H1N1 Swine Flu Update

9-7-2009:   Green Tea, Aging & Lifespan

8-30-2009: Irritable Bowel Syndrome (IBS), Diet & Fiber

8-23-2009: Update on Prostate Cancer and Cryotherapy

8-16-2009: Exercise Improves Lymphedema Symptoms in Breast Cancer Survivors

8-9-2009:   Breast Cancer Recurrence, Death & Vitamin D

8-2-2009:   Honesty, Dishonesty & Brain Function

7-26-2009: Coronary Artery CT Scans & Cancer Risk

7-19-2009: Hormone Replacement Therapy (HRT) & Ovarian Cancer

7-12-2009: Breast Cancer & Metformin (Glucophage)

7-5-2009:   Prostate Cancer & Green Tea

6-28-2009: Air Pollution & the Risk of Deep Venous Thrombosis (DVT)

6-21-2009: Red Yeast Rice, Statins & Cholesterol

6-14-2009: Bone Marrow Stem Cell Transplant & Congestive Heart Failure (CHF)

6-7-2009:   Diet, Soy & Breast Cancer Risk

5-31-2009: Diet and Prostate Cancer Risk

5-24-2009: Diabetes, Glucose Control & Death

5-17-2009: Drug Company Marketing & Physician Prescribing Bias

5-10-2009: Hemorrhoids & Surgery

5-3-2009: Statin Drugs & Blood Clots (Thromboembolism)

4-26-2009: Are We Really Losing the War on Cancer?

4-19-2009:   Exercise in Middle Age & Risk of Death

4-12-2009: Can Chronic Stress Harm Your Heart?

4-5-2009: Does PSA Testing for Prostate Cancer Save Lives?

3-22-2009: CABG Surgery vs. PCI in Diabetics with Coronary Artery Disease; Sweetened Beverages and Coronary Artery Disease

3-15-2009: Depression, Stress, Anger & Heart Disease

3-8-2009: Coronary Artery Disease: CABG vs. Stents?; Swimming Lessons & Drowning Risk in Children

3-1-2009: Aspirin & Colorectal Cancer Prevention; Fish Oil & Respiratory Infections in Children

2-22-2009: Health Differences Between Americans & Europeans; Lycopene & Prostate Cancer

2-15-2009: Statin Drugs & Death Rates; Physical Activity, Breast Cancer & Sex Hormones

2-8-2009: Hormone Replacement Therapy (HRT) & Breast Cancer; Stool DNA Testing & Cancer of the Colon & Rectum

2-1-2009:   Obesity and the Complications of Diverticulosis (Diverticulitis & Bleeding); Obesity, Weight Loss & Urinary Incontinence

1-25-2009: Prostate Cancer, Fatigue & Exercise; Does your Surgeon “Warm-up” Before Surgery?

1-18-2009: Cancer and Vitamins; Teenagers, MySpace and Risky Behaviors

1-11-2009: Exercise Reverses Some Effects of Fatty Meals; Vitamin C and Blood Pressure

1-4-2009: Secondhand Smoke & Heart Attack Risk; Poor Physical Fitness During Childhood & Heart Disease Risk During Adulthood

12-28-2008: Stress & Your Risk of Heart Attack; Vitamin D & the Prevention of Colon & Rectal Polyps

12-21-2008: Breast Cancer Incidence & Hormone Replacement Therapy; Circumcision & the Risk of HPV & HIV Infection

12-14-2008: Vitamin E, Vitamin C and Selenium Do Not Prevent Cancer; Postscript: A Possible Cure for Down’s Syndrome

12-7-2008: Generic vs. Brand-Name Drugs, Stress & Breast Cancer Survival

11-30-2008:   A Possible Cure for Down’s Syndrome?; Smoking & Cognitive Decline; Calcium & Vitamin D & Breast Cancer Risk

11-23-2008:  Breast Cancer & Fish Oil; Lymphedema after Breast Cancer Treatment; Vasectomy & Prostate Cancer Risk

11-16-2008:  Vitamin E & Vitamin C: No Impact on Cardiovascular Disease Risk; Does Lack of Sleep Increase Stroke & Heart Attack Risk in Hypertensive Patients?

11-9-2008:  Statins Cut Heart Attack Risk Even with Normal Cholesterol Levels; Statins & PSA Level

11-2-2008:  Radiation Treatment of Prostate Cancer & Second Cancers; Sexual Content on TV & Teen Pregnancy Risk

10-26-2008:  Smoking & Quality of Life

10-19-2008:  Agent Orange & Prostate Cancer

10-12-2008:  Pomegranate Juice & Prostate Cancer

10-5-2008:  Central Obesity & Dementia; Diet, Vitamin D, Calcium, & Colon Cancer

9-28-2008:  Publication & Citation Bias in Favor of Industry-Funded Research?

9-21-2008:  Does Tylenol® (Acetaminophen) Cause Asthma?

9-14-208:   Arthroscopic Knee Surgery- No Better than Placebo?; A Healthy Lifestyle Prevents Stroke

8-23-2008:  Alcohol Abuse Before & After Military Deployment; Running & Age; Running & Your Testicles

8-12-2008:  Green Tea & Diabetes; Breastfeeding & Adult Cholesterol Levels; Fish Oil & Senile Macular Degeneration

8-3-2008:   Exercise & Weight Loss; Green Tea, Folic Acid & Breast Cancer Risk; Foreign Language Interpreters & ICU Patients

7-26-2008:  Viagra & Sexual Function in Women; Patient-Reported Adverse Hospital Events; Curcumin & Pancreatic Cancer

7-13-2008:  Erectile Dysfunction & Frequency of Sex; Muscle Strength & Mortality in Men; Cryoablation for Prostate Cancer

7-6-2008:  Sleep, Melatonin & Breast Cancer Risk; Mediterranean Diet & Cancer Risk; New Treatment for Varicose Veins

6-29-2008:  Bone Marrow Stem Cells & Liver Failure; Vitamin D & Colorectal Cancer Survival; Green Tea & Colorectal Cancer

6-22-2008:  Obesity, Lifestyle & Heart Disease; Effects of Lifestyle & Nutrition on Prostate Cancer; Ginkgo Biloba, Ulcerative Colitis & Colorectal Cancer

6-15-2008:  Preventable Deaths after Coronary Artery Bypass Graft (CABG) Surgery; Green Tea & Colorectal Cancer; Attention-Deficit/Hyperactivity Disorder (ADHD) & St. John’s Wort

6-8-2008:  Vitamin D & Prostate Cancer Risk; Radiofrequency Ablation (RFA) of Kidney (Renal) Cancer; Antisense Telomerase & Cancer

6-2-2008:  Acute Coronary Syndrome- Do You Know the Symptoms?; Green Tea & Lung Cancer; Episiotomy & Subsequent Deliveries- An Unkind Cut

5-25-2008:  Early Childhood Screening Predicts Later Behavioral Problems; Psychiatric Disorders Among Parents of Autistic Children; Social & Psychiatric Profiles of Young Adults Born Prematurely

5-18-2008:  Can Statins Reverse Coronary Artery Disease?; Does Breast Ultrasound Improve Breast Cancer Detection?; Preventive Care Services at Veterans Administration (VA) Medical Centers

5-11-2008:  Smoking Cessation & Risk of Death; Childhood Traumas & Adult Suicide Risk; “White Coat Hypertension” & Risk of Cardiovascular Disease

5-4-2008:  Super-Size Me: Fast Food’s Effects on Your Liver; Exercise, Weight & Coronary Artery Disease; Contamination of Surgical Instruments in the Operating Room

4-27-2008:  Stents vs. Bypass Surgery for Coronary Artery Disease; The “DASH” Hypertension Diet & Cardiovascular Disease Prevention; Testosterone Therapy for Women with Decreased Sexual Desire & Function

4-20-2008:  BRCA Breast Cancer Mutations & MRI Scans; Bladder Cancer Prevention with Broccoli?; Diabetes: Risk of Death Due to Heart Attack & Stroke

4-13-2008:  Breast Cancer Recurrence & Hormone Replacement Therapy (HRT); Carotid Artery Disease: Surgery vs. Stents?; Statin Drugs & Cancer Prevention

4-6-2008:  Human Papilloma Virus (HPV), Pap Smear Results & Cervical Cancer; Human Papilloma Virus (HPV) Infection & Oral Cancer; Hormone Replacement Therapy (HRT) & the Risk of Gastroesophageal Reflux Disorder (GERD)

3-30-2008:  Abdominal Obesity & the Risk of Death in Women; Folic Acid Pretreatment & Heart Attacks; Pancreatic Cancer Regression after Injections of Bacteria

3-23-2008:  Age of Transfused Blood & Risk of Complications after Surgery; Obesity, Blood Pressure & Heart Size in Children

3-16-2008:  Benefits of a Full Drug Coverage Plan for Medicare Patients?; Parent-Teen Conversations about Sex; Soy (Genistein) & Prostate Cancer

3-9-2008:  Flat Colorectal Adenomas & Cancer; Health Risks after Stopping Hormone Replacement Therapy (HRT); Television, Children & Obesity

3-2-2008:  Medication & Risk of Death After Heart Attack; Hormone Replacement Therapy (HRT) & Mammogram Results; Selenium: Cancer, Heart Disease & Death

2-23-2008:  Universal Healthcare Insurance Study; Glucosamine & Arthritis

2-17-2008:  Exceptional Longevity in Men; Testosterone & Risk of Prostate Cancer; Smoking & Pre-malignant Colorectal Polyps

2-10-2008:  Thrombus Aspiration from Coronary Arteries; Intensive Management of Diabetes & Death; Possible Cure for  Down’s Syndrome?

2-3-2008:  Vitamin D & Cardiovascular Health; Vitamin D & Breast Cancer; Green Tea & Colorectal Cancer

1-27-2008:  Colorectal Cancer, Esophageal Cancer & Pancreatic Cancer: Update from the 2008 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium

1-20-2008:  Testosterone Levels & Risk of Fractures in Elderly Men; Air Pollution & DNA Damage in Sperm; Statins & Trauma Survival in the Elderly

1-12-2008:  Statins, Diabetes & Stroke and Obesity; GERD & Esophageal Cancer

1-7-2008:  Testosterone Supplements in Elderly Men; Colorectal Cancer– Reasons for Poor Compliance with Screening Recommendations

12-31-2007:  Minority Women, Hormone Replacement Therapy & Breast Cancer; Does Health Insurance Improve Health?

12-23-2007:  Is Coffee Safe After a Heart Attack?; Impact of Divorce on the Environment; Hypertension & the Risk of Dementia; Emotional Vitality & the Risk of Heart Disease

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

12-11-2007:  Bias in Medical Research; Carbon Nanotubes & Radiofrequency: A New Weapon Against Cancer?; Childhood Obesity & Risk of Adult Heart Disease

12-2-2007:  Obesity & Risk of Cancer; Testosterone Level & Risk of Death; Drug Company Funding of Research & Results; Smoking & the Risk of Colon & Rectal Cancer

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Dr. Wascher’s Home Page

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Vitamin D is increasingly being looked at as a cancer prevention nutrient, as multiple prior clinical research studies have linked higher blood levels of this hormone-like vitamin, and calcium (which is regulated by Vitamin D), with a decreased risk of colon and rectal cancer, as well as other cancers.Less well understood is the role of Vitamin D as a survival factor in patients who have already been diagnosed with colorectal cancer. Now, a newly updated clinical research study from Harvard University, just published in the British Journal of Cancer, suggests that higher Vitamin D levels in colorectal cancer survivors may be associated with a significantly greater likelihood of surviving the third most common cause of cancer death in the United States.

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Aspirin & Colorectal Cancer Prevention

Fish Oil & Respiratory Infections in Children

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Stress & Your Risk of Heart Attack

Vitamin D & the Prevention of Colon & Rectal Polyps

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BONE MARROW STEM CELLS & LIVER FAILURE

The liver is an extraordinarily complex organ, and is responsible for, literally, hundreds of critical metabolic processes in the body.  While the liver is the only organ that is capable of regeneration in adults, this regenerative capability has its limits, making progressive liver failure a very serious health condition.  When advanced liver failure occurs (most commonly from chronic hepatitis and cirrhosis), a liver transplant is generally the only hope for long-term survival.  Unfortunately, there are far too few donor livers available to go around, and most patients with advanced liver failure will die before a liver transplant becomes available to them (liver failure is currently the 12th most common cause of death in the United States). 

As in other areas of medicine, the emerging field of stem cell therapy has caught the attention of physicians who manage patients with liver failure.  Due to the ongoing ethical debate over the use of embryonic stem cells, which are removed from aborted fetuses, a great deal of research has been done on harvesting a patient’s own stem cells from the bone marrow, and using these cells to repair or replace failing organs.  In what has been widely hailed as a breakthrough in stem cell research, scientists at several different institutions have recently shown that specialized cells for many different organs can be produced from bone marrow stem cells, including the liver.  While bone marrow stem cell research is still in its infancy, the fervent hope of researchers in this field is that failing organs, like the liver, might someday be revived by growing bone marrow stem cells under laboratory conditions that induce them to grow into the cells and, ultimately, the tissues specific to those failing organs.  A new laboratory research study in the journal Gastroenterology, from researchers in Taiwan, and at Emory University, in Atlanta, has now demonstrated that, at least in mice, failing livers can indeed be rejuvenated and rescued with replacement liver cells grown from bone marrow stem cells.

In this innovative study, laboratory mice were treated to induce complete liver failure, which is a uniformly lethal condition.  The researchers then injected liver cells derived from bone marrow stem cells into the mice, as well as bone marrow stem cells themselves (i.e., without first transforming them into liver cells).  These cells were injected into the blood of some of the mice, while other mice received injections of these specialized cells directly into the spleen.  Amazingly, both the stem cells that had been transformed into liver cells and the non-transformed stem cells were subsequently found to be growing in the livers of these mice when they were euthanized at the end of the research experiment, and both types of cells were found to have developed into functional, mature liver cells within the animals’ previously damaged livers.  Even more amazing was the finding that these bone marrow stem cells, whether transformed into liver cells outside of the recipient animals or not, were able to induce liver regeneration and function in mice who had suffered otherwise lethal damage to their livers.  In particular, the mice that had received stem cell injections directly into a vein had more impressive liver regeneration, and return of liver function, than the animals that had received their stem cell injections into the spleen.

In this striking experiment, mice with mortally damaged livers were, effectively, rescued by injecting them with bone marrow stem cells.  These stem cells, including stem cells that were not deliberately transformed into liver cells in the laboratory, then made their way to the animals’ damaged livers, and began to grow and function as normal liver cells, regenerating the animals’ severely damaged livers in the process.  Currently, there are a handful of human clinical trials underway that are working to replicate the dramatic results obtained in this mouse study.  If stem cell therapy, using stem cells taken from a patient’s own bone marrow, can be shown to repopulate failing livers with healthy, functional new liver cells, this would represent an enormous step forward in the management of end-stage liver failure and might, someday, eliminate the need for liver transplants in the majority of liver failure cases.  Similarly, the successful use of stem cells and genetic engineering to, someday, recreate other failing organs (like the heart, kidneys and pancreas, for example) would transform the field of regenerative medicine from something resembling the pages of science fiction books and futuristic movies into a mature technology suited for routine clinical use.  Studies such as this are laying the essential groundwork for a coming revolution in the management of critical organ failure in humans.

 

VITAMIN D & COLORECTAL CANCER SURVIVAL

Colorectal cancer is the third most common cancer in the US, and the third most common cause of death due to cancer.  I have previously reviewed other studies that have suggested that high levels of Vitamin D in the blood may reduce the risk of developing colorectal cancer (please see my recent Archives for my reviews of several such studies).  Although not all studies have confirmed a protective effect of Vitamin D on the risk of developing colorectal cancer, many studies suggest a modest but significant reduction in the incidence of this disease among patients with higher levels of this important vitamin in their blood.  A logical question to ask, then, is whether or not higher levels of Vitamin D in the blood might also be beneficial to patients who have already been diagnosed with colorectal cancer.  A newly reported study, in the Journal of Clinical Oncology, from researchers at Harvard University and the University of South Carolina, may provide an answer to this important question.

In this study, 304 adults participating in the very large Nurses’ Health Study and the Health Professionals Follow-Up Study were diagnosed with colorectal cancer between 1991 and 2002.  As with other participants in these two large public health studies, the patients who were diagnosed with colorectal cancer while participating in the study underwent extensive testing upon entering into the study, including the measurement of blood levels of Vitamin D.  When the researchers compared patient outcomes (i.e., long-term survival versus death), they found that the patients with the highest Vitamin D levels were only half as likely to die, of any cause, during the course of these studies when compared to patients who had the lowest Vitamin D levels.  When comparing the incidence of death specifically due to colorectal cancer according to Vitamin D levels in the blood, this study revealed a trend towards improved survival with higher blood levels of Vitamin D, although this trend did not quite reach statistical significance. 

This study adds to prior studies that have suggested a potentially beneficial role for Vitamin D in reducing both the incidence and mortality of colorectal cancer.  Whether these benefits, if they truly exist, result directly from the effects of Vitamin D itself, or whether a high level of Vitamin D in the blood is simply a marker of other factors that are providing these benefits, is unknown at this time.  (For this reason, taking significant doses of Vitamin D supplements cannot be recommended for colorectal cancer prevention or treatment at this time.) 

Vitamin D supplementation is beginning to find its way into clinical research trials looking at colorectal polyp and colorectal cancer formation, but it will probably be at least 5 to 10 years before definitive, prospective clinical research data becomes available regarding Vitamin D’s true role, if any, in preventing or treating colorectal cancer.  For now, I can only recommend that readers ensure a sufficient intake of Vitamin D, including modest sun exposure (5 to 10 minutes at a time, 2 to 3 times per week, although dark-skinned people may require longer and more frequent sun exposure in order to generate adequate levels of Vitamin D); and moderate intake of foods rich in Vitamin D, including fish (and salmon, in particular), Vitamin D-fortified dairy products and, if you are an aficionado of organ meats, an occasional slice of liver.  At the same time, remember that taking large amounts of Vitamin D supplements may cause very high levels of Vitamin D to accumulate in the blood, which can be toxic and harmful to your health.

 

GREEN TEA & COLORECTAL CANCER

The antioxidant effects of the active compounds in green tea are the focus of tremendous clinical research in the areas of cardiovascular disease and cancer prevention (please see my Archives for my reviews of several important recent studies in this area).  Numerous studies of the “catechins” derived from green tea have suggested that, at least in laboratory animals, green tea catechin supplementation appears to reduce the risk of some types of cancer, including precancerous polyps and cancers of the colon and rectum.  An interesting new study from Columbia University, Cornell University, and Gifu University in Japan, and just now published in the journal Carcinogenesis, extends our understanding of at least one possible mechanism whereby green tea catechins might reduce the risk of developing colorectal cancers, and might even potentially improve survival once colorectal cancer has been diagnosed. 

One important mechanism whereby colorectal cancer cells grow and divide is through a molecule found on the surface of such cells, the epidermal growth factor receptor (EGFR).  When EGFR encounters certain other circulating proteins, including the epithelial growth factor (EGF), the receptor and its growth factor bind together and set off a chemical chain reaction that, ultimately, results in increased tumor cell growth and reproduction.  Indeed, newer “molecularly-targeted” drugs have recently been developed that interrupt EGFR binding to its stimulatory proteins (also known as ligands).

Recent research has shown that the predominant catechin in green tea, epigallocatechin gallate, appears to inhibit EGF binding to the EGFR in Petri dish cultures of human colon cancer cells.  Researchers in this study, therefore, sought to better understand the effects of epigallocatechin gallate on EGFR function, as the EGFR-EGF pathway is an important mechanism whereby cancers of the colon and rectum, and other cancers as well, reproduce themselves and grow.

In this study, researchers treated cultures of human colon cancer cells with epigallocatechin gallate.  They found that even tiny concentrations of this green tea extract resulted in markedly reduced numbers of EGFR on the surface of colon cancer cells, and with as little as 30 minutes of treatment time.  However, this presumably beneficial reduction in EGFR levels on the surface of the cancer cells only lasted 1-2 hours, following 30 minutes of treatment with the green tea extract, before the cells were able to begin restoring the prior number of surface EGFR molecules. 

This study is an important advance in our understanding of how green tea might exert its possible anti-cancer effects at the cellular and molecular levels.  While other potential anti-cancer mechanisms have also been described for green tea and its active components, this particular study focuses on the EGFR-EGF pathway, which is known to be very important for many cancer cells, including colorectal cancer cells, in terms of their survival and progression.  Other studies have also suggested, as this study does, that the effects of individual doses of green tea extracts only persists for a couple of hours, implying that frequent doses of green tea, or its active components, may be required for sustained effect around the clock (alternatively, longer-acting synthetic analogues of these active green tea compounds will have to be synthesized). 

While this particular study offers no proof that green tea might be clinically useful in patients with colorectal cancer, it does very elegantly reveal at least one potential mechanism whereby green tea catechins might be able to exert significant alterations in cancer cell physiology that, in turn, might result in clinically significant benefits for patients diagnosed with colorectal cancer.

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:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at:  rwascher@doctorwascher.net
 

http://www.doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

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OBESITY, LIFESTYLE & HEART DISEASE

There has been much written about the link between obesity and heart disease, and the consensus has generally been that increasing levels of excess weight are associated with increasing levels of coronary artery disease and heart attacks (myocardial infarction).  More recent research studies have attempted to quantify the extent of added risk associated with specific degrees of obesity, and some have also evaluated the benefits, if any, of varying levels of physical fitness among obese patients (please see my Archives for a review of some of these recent research studies).  In general, most of these recent studies continue to show that increasing levels of obesity are associated with increasingly greater risks of coronary artery disease (as well as an increasing incidence of high blood pressure, diabetes, stroke, arthritis, some forms of cancer, and premature death).  While obese people can somewhat reduce health risks with regular and vigorous exercise (the so-called “fit fat” person), most clinical research studies have observed that overall health risks still remain greater than those observed in lean people.  A new study, published in the journal Circulation, evaluates multiple lifestyle factors and their effects on health in obese people.

This study was conducted by researchers from Aarhus University and the Danish Cancer Society, in Denmark, and by researchers from Harvard University in Boston.  Nearly 55,000 men and women participated in the Danish Diet, Cancer and Health Study, and were free of heart disease and cancer upon enrolling in this study.  Participants were 50 to 64 years of age upon entry into this study, and were followed for an average of almost 8 years.  During the course of this study, 1,127 cases of coronary-artery-related complications occurred, including chest pain (angina) and myocardial infarction.  Using body mass index (BMI), a standardized measure of obesity that is based upon weight and height measurements, this study revealed that each additional unit of increase in BMI above the normal range was associated with a 5% increase in coronary artery complications in women, and a 7% increase in men.  As previous studies have shown, obese individuals who regularly engaged in 1 to 3.5 hours of exercise per week had a lower risk of coronary artery disease than obese patients who did not exercise.  Additionally (and not surprisingly), obese smokers had a considerably greater risk of experiencing cardiac events than obese nonsmokers.  Adhering to a heart-healthy diet also appeared to offer some protection against coronary artery disease among obese patients, although the difference in the incidence of coronary artery disease between the “healthiest diet” and intermediate degrees of less healthy diets was essentially nil. 

Taken together, the results from this very large Danish public health study confirm other recent studies that have shown that, even among obese people, lifestyle factors can have a significant influence on cardiac health.  However, none of these positive lifestyle changes, such as exercise, a heart-healthy diet, or abstinence from tobacco, can completely erase the harmful effects of obesity.  There is no substitute for shedding excess weight if you want to maintain your coronary arteries in the best possible shape.  However, if you are already actively working on eliminating excess weight, you can still incrementally decrease your risk of heart disease by adopting a healthy lifestyle while you work towards achieving a healthier BMI.

 

EFFECTS OF LIFESTYLE & NUTRITION ON PROSTATE CANCER

There have been numerous studies on the effects of various nutritional supplements on prostate cancer cells growing in a Petri dish in the laboratory, and in human prostate cancer cells implanted into mice.  However, there is precious little data on the effects of nutritional and other lifestyle interventions, if any, on actual prostate cancer tumors growing in living human beings.  As I have often mentioned before, there have been hundreds of previous research studies that have observed positive responses to experimental treatments in laboratory cell cultures and in mice and rats, but have subsequently failed to show any beneficial impact when applied to human subjects.  However, a new and exciting study, just published in the Proceedings of the National Academy of Sciences, provides a rare glimpse into the effects, at the genetic level, of nutritional and lifestyle interventions on prostate cancer tumor cells taken from the prostate glands of men with this disease.

This very intriguing study was performed by physicians and scientists at the University of California at San Francisco and the Preventive Medicine Research Institute in Sausalito, California, with assistance from the famed J. Craig Venter Institute in Rockville, Maryland.  Initial biopsies were taken from prostate cancer tumors in 30 men who had previously declined surgery or other conventional treatments for their prostate cancers, and all of these men subsequently participated in an intensive nutrition and lifestyle modification program.  In all cases, significant improvements in obesity, elevated blood pressure, and cholesterol levels were observed in these 30 men after 3 months of vigorous exercise, dieting and other healthy lifestyle modifications.  After this 3 month period of intensive lifestyle and nutrition modification, repeat needle biopsies were performed on their prostate cancer tumors.  Both the initial and subsequent prostate cancer biopsy samples were then subjected to specialized genetic testing that compared changes in the activity of individual genes within the tumor cells following 3 months of lifestyle and nutrition modification.

Gene expression profiling revealed that the activity of 48 individual genes had significantly increased following completion of the 3-month lifestyle modification program, while 453 genes had become less active.  The researchers then looked at all of the 501 genes that had undergone changes in their levels of expression, and assessed their functions as they related to cancer cell growth and progression.  After analyzing the functions of these 501 genes, the researchers determined that many of them were directly involved in critical pathways used by cancer cells to grow and divide.

Although this was only a small pilot study, it is one of only a handful of “in vivo” clinical research studies that have objectively studied the impact, at the level of gene activity, of healthy lifestyle modifications on active cancers growing within living human beings.  As such, the implications of this study’s findings are potentially enormous.  Although it is not possible to tell if these 30 men will experience a reduction in the growth or spread of their cancers as a result of these lifestyle modifications, the objective improvement in the “genetic profile” of their prostate cancers, following 3 months of intensive diet and exercise modification, is an exciting finding in and of itself.  The implications of this study’s results offer hope that rigorous lifestyle modifications may help to both prevent some cancers and to reduce the biological aggressiveness of cancers that have already developed.  However, this is only a small “proof of concept” research trial.  A larger randomized clinical research trial will now have to be performed using a similar approach, but with a “control group” of patients who do not undergo any lifestyle or nutrition modifications.  Additionally, this future randomized study will have to follow all of the participating patients for a sufficiently long period of time to allow any clinically significant differences between patient groups to become evident.  Meanwhile, this fascinating little study offers a tantalizing look (at the genetic level) at the potential impact of diet and lifestyle changes on the biology of cancer cells growing within the human body.

 

GINKGO BILOBA, ULCERATIVE COLITIS & COLORECTAL CANCER

For the most part, the anti-inflammatory and anti-cancer effects of herbal supplements and vitamins with known antioxidant activity have turned out to be quite disappointing in human research trials, despite favorable results from previous laboratory research using cell cultures and laboratory mice and rats. 

The ginkgo biloba tree is an ancient plant with no known living relatives, and is often described as a “living fossil.”  Some living ginkgo trees in china are estimated to be nearly 3,000 years old, and fossilized specimens of this unique tree are numerous.  For thousands of years, the unique bi-lobed leaves of the ginkgo tree have been used for medicinal purposes, initially in traditional Chinese medicine, and more recently, throughout the remaining world.  Ginkgo leaves are known to possess antioxidant activity, converting cell-damaging “free radical” oxygen molecules, which are potentially toxic byproducts of normal metabolism, into less toxic substances.  A new study published in the journal Carcinogenesis has evaluated the effects of ginkgo biloba extract in preventing and treating inflammatory colitis in mice.  This study, from laboratories at the University of South Carolina and McGill University, in Canada, sought to demonstrate whether or not ginkgo biloba might be useful in preventing or treating ulcerative colitis, a chronic inflammatory disease of the rectum and colon associated with an increased risk of cancer development in humans.

In this study, inflammatory colitis was induced in laboratory mice.  The group of mice that was fed a standardized extract of ginkgo biloba had much lower levels of inflammatory substances in their circulation than the mice that were not given the ginkgo supplement.  Moreover, much lower numbers of immune cells associated with immune-mediated inflammation, known as CD4+ T-lymphocytes, were present in the mice that had received ginkgo supplements.  The activation of macrophages, which also participate in the inflammatory response, was also significantly reduced in the mice that received ginkgo biloba.  In this study, the use of ginkgo biloba extract was found to significantly decrease the degree of inflammatory colitis in this mouse model of ulcerative colitis. 

At this time, there are no active clinical trials assessing the effects of ginkgo biloba in human patients with ulcerative colitis, or other inflammatory bowel diseases, such as Crohn’s disease.  Based upon the intriguing results of this laboratory study, a human clinical trial to assess ginkgo biloba in patients with inflammatory bowel disorders should be initiated now.

 

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PREVENTABLE DEATHS AFTER CORONARY ARTERY BYPASS GRAFT (CABG) SURGERY

A great deal of attention is being directed at reducing preventable complications and deaths following surgery.  Because so much clinical data is available for coronary artery bypass graft (CABG) surgery, it has long been used a model for studying risk reduction following surgery. 

As an important aside, increasing pressure is being exerted upon surgeons and hospitals to achieve high levels of compliance with specific “quality of care” parameters that have been put into place by Medicare and other large healthcare insurers.  Although these criteria have already become etched in stone, many of them of have been implemented despite a lack of any high level research evidence showing a direct correlation between these benchmarks and clinical outcomes.  There are already some very strong feelings among many physicians and hospital administrators regarding the imposition of these new “quality improvement” guidelines in the absence of compelling research data to support them.  A new research paper in the journal Circulation adds more fuel to the fires burning over this very controversial topic.

For CABG operations, and for several other complex, high-risk operations, cumulative death rates following surgery have long been used as a surrogate measure of overall quality of care.  Indeed, mortality rates for CABG surgery at individual hospitals can, increasingly, be found published on websites sponsored by the healthcare insurance industry and other groups.

In this study from Ontario, Canada, a retrospective analysis of 347 randomly selected in-hospital deaths following CABG surgery at 9 Canadian hospitals was performed.  Two expert consultant heart surgeons reviewed summaries of the charts from these patients while being blinded to patient identification as well as both the operating surgeons and the hospitals involved in the care of these patients.  In those cases where the 2 expert reviewers were not in complete agreement, a third cardiac surgery consultant was also brought in.

Among all 9 hospitals, the overall risk of death associated with CABG surgery was a very impressive 1.3 to 3.1%.  However, when the cardiac surgeon consultants completed their analysis of these 347 perioperative deaths, they determined that 111 of them, or 32%, were preventable (in 86% of these deaths, problems in the operating room were found to have contributed to the death of patients, while 61% of the deaths appeared to have also involved problems in the intensive care unit following surgery).  Both primary reviewers jointly agreed that 32% of the patient deaths appeared to involved deviations in established perioperative care guidelines, while 42% of the deaths were considered by at least 1 reviewer to have involved significant deviations from established care guidelines.

I find the results of this study to be simultaneously stunning and confirmatory to what I—and many other surgeons—intuitively believe.  While all of us strongly desire to drive complication and death rates after surgery to the lowest possible achievable numbers, many of the current indicators of “quality of care” that have been implemented thus far are probably not valid tools for monitoring the very events that they were designed to detect.  Regarding preventable perioperative deaths following CABG surgery, specifically, this provocative study found absolutely no correlation between the overall mortality statistics at 9 different hospitals and the presence of a large percentage of apparently preventable deaths, and despite the current and routine use of overall mortality rates as the primary benchmark of “quality of care.”

The findings of this study are important, and suggest that we need to find better indicators of preventable complications and deaths other than the currently standard of overall mortality.  With the enormous pressures facing all aspects of healthcare in the United States today, we simply cannot afford to base critically important healthcare quality- and performance-improvement decisions upon faulty and inaccurate statistical benchmarks.  The results of this study should serve as a wake-up call to both the healthcare insurance industry administrators who have imposed these faulty standards upon all of us; as well as physicians and administrators, the vast majority of whom genuinely desire to deliver the highest possible quality of care to their patients.

 

GREEN TEA & COLORECTAL CANCER

Much has been written about the potential anti-cancer effects of green tea, including the many research studies that I have reviewed in this column (please see my archives, below).  A new research study, just published in the journal Gastroenterology, adds additional important information to our understanding about the effects of green tea, and its active ingredients, on the development and progression of cancer.

Researchers from the University of Tennessee performed several interesting experiments using epigallocatechin-3-gallate, the predominant active compound in green tea.  This extract of green tea was first applied to human colorectal cancer cells growing in a culture dish.  A series of complex laboratory tests determined that the green tea extract significantly reduced the presence of the protein basic fibroblast growth factor, which has been implicated, along with several other proteins, in tumor cell growth and spread (metastasis). 

In the second part of this study, mice with a genetic defect that results in a 100% risk of colorectal cancer had their diet supplemented with the green tea extract (while a control group of similar mice did not receive this supplement).  Once again, the researchers found that the mice treated with the green tea extract had decreased levels of basic fibroblast growth factor in their colorectal tumor cells.  Moreover, supplementation with green tea extract resulted in considerably fewer colorectal tumors when compared with the mice that did not receive the extract. 

The results of this study provide intriguing insight into the potential caner prevention effects of green tea, and at the molecular level.  Several human clinical trials are already underway, looking at the effects of green tea on cancer prevention and cancer treatment.  As we have seen with other areas of clinical research, what works in Petri dishes and laboratory mice doesn’t always translate well to humans.  It will be interesting to see what the long-term results of ongoing human green tea clinical trials will tell us about the potential disease prevention and therapeutic effects of green tea.     

 

ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD) & ST. JOHN’S WORT

Parents of children with ADHD are, understandably, reluctant to see their children take the powerful stimulant drugs that are most commonly prescribed for this condition.  As with many other illnesses, people often turn to herbal supplements and other “natural remedies” as an alternative to prescription medicines.  St. John’s Wort, also known by its scientific name, Hypericum perforatum, is a plant with worldwide distribution, and has been touted as a remedy for a variety of ailments, including ADHD.

A new prospective, randomized, double-blinded study, just published in the Journal of the American Medical Association, reports on the effects of St. John’s Wort supplements on children and adolescents with ADHD.  The design of this research study conformed to the highest achievable level of clinical research in that neither the patients nor the researchers knew who was receiving St. John’s Wort and who was receiving a placebo (sugar) pill of identical appearance until after the study was over.  Researchers from the following institutions participated in this study: the School of Naturopathic Medicine at Bastyr University in Washington, the University of Washington, the Massachusetts General Hospital, and Harvard University.

In this study, 54 children and adolescents with ADHD were randomly assigned to receive either St. John’s Wort or a placebo pill 3 times per day, for 8 weeks.  No other ADHD medications were permitted during the course of this clinical research study.  At the end of the study, all patients underwent reevaluation of their ADHD.  One of the patients withdrew from the study due to side effects from the pills, leaving 53 patients who completed the entire study.

Unfortunately, there was no discernible difference between the two groups of children in terms of inattentiveness and hyperactivity.  In fact, there was no significant difference in overall ADHD scoring between the group of children who received St. John’s Wort and those who received the inactive placebo pills. 

The findings of this study are, unfortunately, consistent with an increasing number of other recent high-quality clinical research trials that have looked at St. John’s Wort, and other herbal or “natural” remedies, for the prevention or treatment of various diseases.  Before these kinds of clinical research trials were performed, the largely unregulated sales and promotion of dietary supplements allowed manufacturers to make almost any health claims they wanted, as long as they included the necessary disclaimer indicating that the FDA had not assessed the validity of any such claims.  Even today, the multi-billion dollar supplements industry remains almost completely unregulated, except with regards to industrial hygiene at their manufacturing plants.  Fortunately, the scientific world is taking a greater interest in evaluating many of these supplements.  Hopefully, this kind of research will not only debunk the often absurd claims made for the beneficial effects of dietary supplements by their manufacturers but, perhaps, will also validate the potential health benefits of at least some of the hundreds of different supplements currently being produced and sold. 

Unfortunately, this particular study, although rather small, was well-designed and conducted, and it did not find any apparent benefit associated with St. John’s Wort in children and teenagers with ADHD.  

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:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at:  rwascher@doctorwascher.net
 

http://www.doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

 

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VITAMIN D & PROSTATE CANCER RISK

I have reported on previous clinical research studies suggesting that increased levels of Vitamin D in the blood may be associated with a lower risk of certain cancers (and colorectal and prostate cancer, in particular). I have also previously summarized my view that the epidemiological data supporting a cancer-protective effect for Vitamin D is relatively weak, and that the available body of research on this topic contains the findings of multiple studies that appear to contradict each other. Now, a newly reported study in the Journal of the National Cancer Institute adds to this body of clinical research literature on Vitamin D and prostate cancer prevention.

This research was performed by investigators from the National Cancer Institute, the University of Washington, and the University of Alabama. This research study was part of a larger study known as the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Study. This study included 749 patients who developed prostate cancer during the course of the study, as well as 781 control patients who did not develop prostate cancer (all male patients who participated in this study underwent annual screening for evidence of prostate cancer). At the onset of this clinical research trial, and before any of these patients were diagnosed with prostate cancer, blood was analyzed for various factors, including Vitamin D levels. Unfortunately, the results of this study were somewhat disappointing in view of previously published studies showing that high levels of Vitamin D in the blood appeared to be associated with a lower risk of prostate cancer.

In this study, higher levels of Vitamin D in the blood did not appear to have any protective effect, whatsoever, against developing prostate cancer. In fact, on the contrary, among those patients diagnosed with prostate cancer during this clinical research trial, higher levels of Vitamin D in the blood appeared to be mildly associated with more aggressive cancers.

The findings of this rather large, prospective clinical trial will be disappointing to those who have believed that increased levels of Vitamin D in the blood might protect against the onset of prostate cancer. While Vitamin D has been shown to reduce prostate cancer cell growth in laboratory studies, the results of human studies have been less compelling and less consistent.

Although the findings of this study suggests that very high levels of Vitamin D in the blood of patients already diagnosed with prostate cancer might be associated with more aggressive tumors, the correlation between blood levels of Vitamin D and tumor aggressiveness was not uniform, suggesting that this observation has not been definitively proven by the data derived from this study. Another limitation of this particular study is that Vitamin D levels in the blood were only measured a single time during the course of this study (at the beginning of the study). It is, therefore, not possible to know whether or not Vitamin D levels might have fluctuated considerably during the period of several years when this study was being carried out.

According to American Cancer Society estimates, more than 186,000 American men will be diagnosed with prostate cancer in 2008, and nearly 30,000 will die of the disease. Most men should begin annual screening for prostate cancer at age 50, which includes digital rectal examination and the measurement of the prostate specific antigen (PSA) level in the blood. Men at increased risk of developing prostate cancer, including African-American men and all men with a significant family history of the disease, should begin annual screening at age 45. Also, obesity and a high-fat diet have been linked to an increased risk of developing prostate cancer. Exercise, eat well, and get screened ever year, please.

As for Vitamin D supplements, the overall human clinical data, to date, has not been very compelling with regards to prostate cancer prevention. However, there are a handful of ongoing clinical research trials looking at the effects, if any, of Vitamin D supplementation on prostate cancer risk. Unfortunately, it may be 5 to 10 years before any substantial results are available from such studies.

RADIOFREQUENCY ABLATION (RFA) OF KIDNEY (RENAL) CANCER

Approximately 50,000 new cases of kidney (renal) cancer will be diagnosed in 2008, and more than 13,000 people will die of the disease, according to American Cancer Society estimates. Not too many years ago, even patients with very small tumors isolated within the kidney faced removal of the entire kidney. With only one remaining kidney, many patients faced the prospect of declining kidney function later in life as a complication of diabetes, untreated hypertension, and other disease that affect kidney function. In recent years, patients with small, localized kidney cancers have, increasingly, been able to undergo partial removal of the affected kidney, based upon clinical research data showing no significant differences in terms of survival or cancer recurrence with either treatment option. As is the case with complete removal of the kidney (total nephrectomy), however, even partial removal of the kidney requires a major surgical operation. Increasingly, partial or total removal of the kidney can be achieved using modern minimally-invasive procedures that reduce the amount of postoperative discomfort and recovery time. However, these minimally-invasive approaches still carry similar risks of complications when compared to traditional open surgical approaches.

A relatively recent innovation in the minimally-invasive treatment of tumors within solid organs (including the kidneys) has generated a lot of interest in the clinical world. Radiofrequency ablation (RFA) is a technique whereby tumors in the kidney, liver and lung can be treated, or “ablated,” by inserting long needles into the tumors and heating them with radiofrequency current (I employ this same technique to destroy otherwise unresectable tumors of the liver). In many cases, RFA of the kidney can be performed under sedation in the Radiologist’s office, while using a CT scanner or ultrasound machine to guide the ablation needle into the target tumor.

One glaring limitation of RFA is that, unlike the surgical removal of a tumor, one cannot reliably assess the adequacy of RFA treatment under a Pathologist’s microscope, as none of the tumor or surrounding tissues are removed from the patient. This has led to some concern about the use of RFA as primary, definitive treatment for solid organ tumors, except in those cases where such tumors cannot be completely or safely removed by a surgeon. Although an array of sophisticated scanners can be used to observe solid organs previously treated with RFA, none of these scans can detect microscopic residual traces of cancer cells that may lead, in time, to cancer recurrence and spread.

A new research study, just published in the journal Urology, looked at the impact of RFA on small kidney cancers at least one year following RFA treatment. In this small clinical study, 19 patients who had previously undergone RFA of their small kidney cancers, at least 1 year previously (average follow-up after RFA treatment was, in fact, about 29 months), and who had no evidence of recurrence on subsequent CT scans, underwent needle biopsies of the RFA ablation site to assess for residual or recurrent cancer.

In this small study of patients with no clinical evidence of recurrence, at least by serial CT scans, of their kidney cancers, all kidney needle biopsies revealed only dead, nonviable scar tissue.

While the results of this very small study are tantalizing, some caution in interpreting its results is in order. The most common type of kidney cancer (renal cell carcinoma) is somewhat unusual, compared to most other cancers, in that cancer recurrence can begin to show up in the body many years after initial diagnosis and treatment (and after apparent cure). And so, even with an average follow-up of just over 2 years in this study, it is difficult to say what the long-term success rate of RFA will look like in these patients.

Another caveat to the otherwise good news contained in this study is the issue of sampling error. Because only a very small sample of tissue is recovered during needle biopsies, “false negative” results can arise because an area of viable tumor cells might be missed by the biopsy needle.

These concerns aside, the results of this study at least suggest that highly selected patients with small kidney cancers that are anatomically suitable for RFA ablation might be able to avoid surgery if their post-RFA CT scans show no evidence of residual or recurrent cancer. Unfortunately, this very small retrospective study of highly selected patients cannot definitively tell us if RFA is an equivalent treatment to the current surgical methods used to manage this cancer.

Fortunately, there are at least 3 ongoing or recently completed clinical trials comparing RFA with partial nephrectomy in patients with early stage kidney cancer. If the long-term results of these studies are favorable, then the treatment of small, early kidney cancers might undergo yet another revolution in terms of further minimizing the invasiveness of treatment.

ANTISENSE TELOMERASE & CANCER

Without getting too bogged down into the arcane disciplines of molecular biology and genetics, telomerase, a protein manufactured in all healthy cells, restores the frayed ends of our chromosomes that arise each time a cell (and its complement of 46 chromosomes) divides. Unfortunately, most of the mature cells of our body do not produce significant quantities of this enzyme. Furthermore, as our cells age (and thus as we age), the DNA repair systems present in each of our approximately 60 billion cells becomes increasingly less accurate and less effective, and the cumulative fraying of the ends of our chromosomes eventually leads to a phenomenon known as the Hayflick limit. Basically, the Hayflick limit is reached when the ends of chromosomes become so frayed that cells can no longer divide, and the cell is then shunted into a cell death mode. Such cells in our bodies are then said to undergo senescence, and many of the effects of advancing age are the direct result of this phenomenon.

While significant telomerase levels are not seen in most mature cells of the body, increased activity of this enzyme has been observed in more than 90% of cancers that have been studied, and the presence of this protein in cancer cells is thought to be an important underlying reason for their acquired immortality.

A newly published study in the European Journal of Cancer Prevention reports on a fascinating new approach to cancer therapy. In this study, Chinese researchers designed an “antisense” telomerase gene which was, essentially, a mirror image of the normal telomerase gene. When this antisense gene is copied into the RNA template used to code for the creation of proteins (all enzymes are proteins, by the way), instead of actually coding for the telomerase protein, the antisense telomerase RNA molecule tightly binds with the normal telomerase RNA, thus reducing the production of this “immortalizing” protein in cells where the antisense telomerase gene has been inserted.

In this particular study, the researchers inserted the antisense telomerase gene into stomach cancer cells, and they then observed a dramatic reduction in the rate of cell growth and division in the treated cancer cells due to reduced levels of the telomerase enzyme. When these stomach tumor cells were implanted into immune-deficient mice, the untreated cells rapidly grew and developed into cancerous tumors. However, when the cancers cells treated with the antisense telomerase gene were implanted into mice, there was no apparent development of tumors.

This study is highly intriguing in that it reveals that a “molecularly targeted” approach to reducing cancer cell growth and division can, at least in mice, remarkably inhibit the growth of such cells into disease-causing tumors. Since most of the mature cells in our bodies do not manufacture significant levels of telomerase, while most cancer cells do, telomerase inhibition may hold some promise of being able to convert cancer cells’ malignant behavior into something more resembling normal, benign cells. Whether or not this same approach will work in humans is not yet clear. Additionally, there have been serious setbacks, and complications, recently in several human gene therapy research trials. However, the results of this innovative laboratory study raise the hope that, one day, most cancers will either be completely curable by molecularly-targeted therapies or, at least, be converted into stable, non-progressive diseases that can be controlled indefinitely with these types of emerging therapies.

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:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at: rwascher@doctorwascher.net

http://www.doctorwascher.com

Copyright 2008. Robert A. Wascher, MD, FACS.

All rights reserved.

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ACUTE CORONARY SYNDROME- DO YOU KNOW THE SYMPTOMS?

The acute coronary syndrome (ACS) describes patients who are experiencing symptoms of inadequate blood flow to the heart (myocardial ischemia), or who are experiencing an actual heart attack (myocardial infarction).  Patients who are experiencing ACS should see a qualified emergency room or cardiology physician immediately, as there is abundant research evidence showing that the early diagnosis and treatment of ACS leads to improved survival, and improved heart function in survivors.

Most of us know the classic g and symptoms of ACS, including the acute onset of crushing chest pain, which sometimes radiates to the left arm or the left jaw.  However, for many patients with heart disease, ACS can present without these classic “textbook” symptoms.  These atypical ACS symptoms can include any of the following: isolated pain (i.e., without chest pain) in the right or left arm, upper back, neck, jaw or upper abdomen (the latter is often perceived as “indigestion”); shortness of breath; the new onset of weakness or extreme fatigue; fainting or the feeling that one is about to faint; nausea or vomiting; and palpitations or other abnormal heart rhythms (patients with diabetes and elderly patients are more likely to experience these atypical signs and symptoms, rather than the classic signs and symptoms associated with ACS).

Certainly, it is understandable that many lay people who have no personal history of coronary artery disease might not be aware of the atypical signs and symptoms of ACS, but one would think that patients with a known history of myocardial ischemia or prior myocardial infarction would have a pretty fair idea regarding both the typical and atypical signs and symptoms of ACS.  However, a clinical study, just published in the journal Archives of Internal Medicine, suggests that almost half of patients with a history of ischemic heart disease were ill-informed about the signs and symptoms of ACS.

This multi-institutional study was conducted by researchers at the University of California (the San Francisco and Los Angeles campuses), the University of Pennsylvania, the University of Washington, the University of Kentucky, the University of Nevada (Reno), and other institutions in the United States and Australia.  In this clinical study, 3,522 patients with a history of either heart attack or a prior medical intervention for coronary artery disease participated in a survey designed to assess their knowledge about the symptoms of ACS, as well as the appropriate steps that should be taken by patients experiencing the symptoms of ACS.  The average age of these patients was 67, and 68% of these study volunteers were men.

The researchers defined a score of less than 70% on the survey as being representative of a low level of knowledge.  The average score among all of these adults with a history of significant coronary artery disease was only 71%.  Moreover, the scores of 46% of the participating patients, or nearly half of the patients, fell within the “low knowledge” range!  When the researchers analyzed factors that were associated with higher knowledge scores on the survey, they found that the following factors were statistically significant predictors of adequate or excellent knowledge about the symptoms of ACS:  female gender, younger age, higher levels of education, previous participation in a cardiac rehabilitation program, and receiving care by a cardiologist rather than an internist or general practitioner.  A prior history of heart attack or coronary artery bypass surgery (ABG) was not associated with a higher level of knowledge as tested by the survey, however. 

The results of this clinical study are rather provocative, and suggest that more needs to be done to educate patients at high risk of experiencing ACS, including those who have already experienced episodes of ACS in the past.  When ACS occurs, delays in diagnosis and treatment can truly become a matter of life-and-death.  If you believe that you are experiencing the symptoms of ACS, then please do not ignore them.  Instead, you should seek appropriate medical assistance, and without delay!

 

GREEN TEA & LUNG CANCER

Lung cancer remains the most common cause of cancer-associated death in the United States more than 40 years after the link between smoking and lung cancer was first publicly disclosed by the US Surgeon General.  In 2008, the American Cancer Society estimates that approximately 215,000 new cases of lung cancer will be diagnosed (almost evenly split between men and women), and about 166,000 Americans will die of this highly lethal cancer.  The greatest tragedy surrounding this greatest of cancer killers is that more than 95% of lung cancer cases could be preventing simply by eliminating smoking.  When I hear people complain that the war on cancer has not delivered dramatic reductions in the incidence of most cancers, I immediately think about lung cancer.  In 2008, and there will be an estimated 566,000 deaths due to cancer in the United States, and more than 166,000 of these deaths, or 29% of all cancer deaths, will be due to a cancer that is almost completely preventable (i.e., simply by leading a reasonably healthy lifestyle)….  For these reasons, and because the available treatments for most cases of lung cancer are rarely successful in eradicating all traces of cancer, I rarely include reviews of lung cancer research clinical studies in this column.  However, an intriguing research paper, just published in the journal Carcinogenesis, looks at the effects of an extract of green tea upon lung cancers induced in laboratory mice.  This study was conducted by researchers from the University of Cincinnati, the University of Minnesota, and Washington University.

In this laboratory study, a decaffeinated extract of green tea leaves was added to the diet of mice after they were injected with a mutagenic chemical known to cause lung cancer in mice. A control group of additional mice received injections of the cancer-causing chemical, but did not receive the green tea extract in their diet.  While green tea extract supplementation did not appear to reduce the overall number of lung cancer tumors that developed in the mice, it did appear to significantly reduce the maximum size of the lung tumors when compared to the tumors that developed in the control group of mice.  Using both MRI scans of the lung tumors and microscopic evaluation of lung tumors after the mice were euthanized, the researchers confirmed that the mice that had received green tea extract supplementation had significantly smaller tumors than the untreated control group mice.

While green tea extract did not appear to prevent the development of lung cancer in mice treated with a chemical (benzo[a]pyrene, which is also present in cigarette smoke) known to induce this type of cancer in laboratory mice, dietary green tea did appear to reduce the progression of the resulting lung tumors.  As with all animal-based research studies, however, extrapolating the effects of various treatments on laboratory animals to humans requires a big leap of faith.  In some cases, humans do respond in similar ways as has been observed in laboratory animals.  In many other cases, what appears to work in mice turns out not to work (at least to any clinically significant degree) in people.  However, this research article joins hundreds of others that suggest a modest-to-moderate anti-tumor effect associated with green tea polyphenols for at least some types of cancer.  Currently, there are 25 registered clinical research trials underway in the United States that are looking at the effects of green tea supplements on the development and progression of various types of cancer, including lung cancer.  Hopefully, at least some of these trials will confirm a beneficial effect of green tea supplementation in humans, as has previously been observed in cell cultures and animal studies.  Meanwhile, please do your part in the war against cancer.  If you don’t currently smoke, then please don’t start.  If you already smoke, then please quit, now.

EPISIOTOMY & SUBSEQUENT DELIVERIES- AN UNKIND CUT

Increasingly, obstetricians, and their patients, are questioning the traditional wisdom about routinely performing episiotomies in the delivery room.  An episiotomy involves making an incision on the edge of the vaginal wall and perineum as the baby’s head descends within the vaginal birth canal.  In theory, the episiotomy is a “controlled” laceration of the highly sensitive perineal tissues between the vagina and rectum, and was originally thought to reduce the incidence of deep tears of these tissues, including the sphincter muscles of the anus and rectum.  (After the baby is born, the episiotomy is then repaired by the obstetrician with sutures.)  However, in recent years, the beneficial effects of episiotomy, if any, have increasingly been called into question.  In fact, recent clinical research studies have confirmed what many new mothers, their husbands, and even many obstetricians, have long suspected, and that is that episiotomies often appear to cause the very same injuries and long-term complications that they are intended to prevent.  These complications can leave women incontinent, and with chronic perineal pain that often interferes with their ability to comfortably have intercourse for months, and sometimes for years.  Ask any new mother (or her husband) who has delivered children both with and without an episiotomy which delivery left her with the greatest amount of perineal pain, and for the longest amount of time…. 

If, as it is becoming apparent, episiotomies do not prevent perineal and anal sphincter complications during most routine deliveries, then what might the effects of episiotomies be during subsequent births?  A new research paper in the journal Obstetrics & Gynecology provides some answers to this question.  The researchers reviewed the medical records of more than 6,000 women who underwent at least two consecutive vaginal deliveries at the University of Pittsburgh.  They found that 48% of these women underwent episiotomy with their first delivery.  The researchers then compared the incidence of complications among these women who had received episiotomies with the remaining 52% of women who did not undergo episiotomy during their first delivery.  The results were both striking and concerning.

Among the women who had previously received an episiotomy, 51% experienced moderately severe perineal lacerations during their subsequent second vaginal delivery, while only 27% of the mothers who had not undergone a previously episiotomy suffered similar perineal lacerations.  Severe lacerations that involved the anal sphincter muscle (and which can lead to painful bowel movements and incontinence) occurred in almost 5% of the women who had previously undergone an episiotomy versus just under 2% of the women who had not received a previous episiotomy. 

In summary, this retrospective clinical study adds to a growing body of research suggesting that episiotomy almost certainly does more harm than good, at least for relatively routine deliveries.  In fact, the very birth-associated complications that episiotomy is supposed to prevent are actually more common in women who have been subjected to this procedure than in those who have not received an episiotomy.  While there may still be an occasional indication for episiotomy if the vaginal canal cannot safely accommodate and deliver a large or malpositioned baby, in the vast majority of cases of otherwise normal and spontaneous vaginal delivery, there appears to be no clinically valid reason, any longer, for episiotomy. 

If you are pregnant, it might be wise to raise this issue with your obstetrician, as many obstetricians who continue to routinely perform episiotomy consider the procedure to be an integral part of their obstetric care, and some obstetric physicians may, therefore, plan to perform this generally unnecessary, and potentially harmful, surgical procedure without first discussing it in detail with their patients. 

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:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at:  rwascher@doctorwascher.net

http://www.doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

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SMOKING CESSATION & RISK OF DEATH

Smoking, as we all know, is associated with an increased risk of cancer, cardiovascular disease, non-cancer lung disease, and early death.  It is also widely known that smoking cessation will, over time, lead to a reduction in smoking-associated health risks.  However, the extent of this reduction, and the duration of smoking cessation required to realize significant health benefits, has not been entirely clear.  Now, a new clinical research study from the Washington University School of Medicine and Harvard University, and published in the Journal of the American Medical Association, provides important data that directly addresses these critical questions.  This study was part of a much larger overall study, the Nurses’ Health Study, and includes more than 100,000 female nurses who have participated in this prospective clinical research trial since 1980. 

In this particular clinical study, a total of 12,483 women died during the course of the parent study.  Among the women who died, 36% were “never-smokers,” 29% were active smokers, and 35% were prior smokers who had previously quit.  When all 104,519 women participating in this huge study were evaluated, active smokers were found to be almost 3 times more likely to die (of any cause) than “never-smokers.”  When the researchers looked at the incidence of cancers known to be associated with smoking, the active smokers had more than 7 times the risk of these cancers than were observed among the women who have never smoked.  Even those cancers not definitively associated with smoking were still more commonly observed among the active smokers, occurring approximately 1.6 times more frequently in this group when compared to the “never-smokers.”  When compared to “never-smokers,” the incidence of colon and rectal cancer was observed 1.6 times more frequently among the women who were active smokers, and 1.2 times more often among the women who had smoked in the past but previously quit.  Death due to lung disease (other than cancer) was (not surprisingly) also significantly more common among the women who were active smokers.

Based upon the results of this long-term prospective study, a full 20 years of smoking cessation was necessary before death rates in previous smokers fell to the level observed among “never-smokers.”  Strikingly, when the actual causes of death were assessed, this study concluded that 64% of the deaths observed among the actively smoking women were directly attributable to cigarette smoking, while 28% of the deaths observed among the former smokers were smoking-related.

This study is very valuable from a public health perspective, as it relies upon a very well designed and managed prospective clinical research trial, with long-term follow-up, to provide high quality clinical data.  In doing so, the statistics derived from this study are both sobering and likely to be valid.  What is abundantly clear is that smoking is a potent cause of otherwise preventable and early deaths.  What is also clear is that the earlier one starts smoking, and the longer one continues to smoke, the greater the risk of chronic illnesses and early death.  On the other hand, quitting smoking can, over time, reduce the excess risk of illness and death associated with smoking.  This risk reduction begins immediately after smoking cessation, but it appears to take approximately 20 years before all of these smoking-related health risks disappear entirely.  The lesson is simple, really.  You are much better off, health-wise, if you never start smoking.  However if you are already a smoker, quitting (and quitting right now) will allow you to begin that long but worthwhile journey back to the level of health risk that you would otherwise have enjoyed had you never started smoking in the first place.

CHILDHOOD TRAUMAS & ADULT SUICIDE RISK

The experiences that we have during the pivotal developmental years of our childhood can have an enormous impact on our adult lives.  Many among us struggle, consciously or subconsciously, late into life with the adverse experiences of our early years.  A new clinical study from the University of California at San Diego, and from several medical centers in Canada, and just published in the American Journal of Public Health, further illuminates this very private arena of our lives, and the results of this study are rather sobering.  Using data from a large mental health study, sponsored by the National Institutes of Health, in which nearly 10,000 adult men and women volunteered to take a detailed survey within their homes, this particular research study was designed to assess the impact of childhood traumas on mental health and suicide risk during adulthood.  The specific types of adverse childhood experiences assessed included physical abuse, sexual abuse, and the witnessing of domestic abuse. 

Based upon the data collected during this study, the researchers estimated that 22% to 32% of the psychiatric disorders observed in the women volunteers were associated with adverse childhood events, while 20% to 24% of the mental illness observed in the male volunteers appeared to be associated with traumatic childhood experiences.  Suicidal thoughts and actual suicidal attempts in women appeared to be linked to adverse childhood events in 16% and 50% of such cases, respectively, and in 21% and 33% of men, respectively.  Increasing numbers of traumatic events experienced during childhood also appeared to be associated with an increasing risk of psychiatric illnesses and thoughts of suicide (or actual suicidal attempts). 

While mental health studies, such as this one, rely on far more subjective findings than most non-psychiatric clinical research studies, the results of this study nonetheless provide at least a semi-quantitative estimate of the contribution of traumatic childhood illnesses to those people already suffering from mental illness, including those who have either contemplated or actually attempted suicide.  While there are many among us who have suffered tremendously adverse experiences during childhood, and who nonetheless have progressed into adulthood without any obvious evidence of any mental health difficulties, clearly, there many people who continue to struggle with the impact of such early-life experiences throughout their adult lives.  If you are one of those people who struggle with depression, poor self-esteem, chronic anxiety, or other troubling symptoms of poor mental or emotional health, then I urge you to seek help from your personal physician, or from a mental health professional.  The same goes for the thousands of young men and women who are returning from the battlefields of Iraq and Afghanistan with post-traumatic stress disorder symptoms.  If you are feeling badly, please get help, now.

“WHITE COAT” HYPERTENSION & CARDIOVASCULAR DISEASE RISK

Most physicians are very familiar with the “White Coat Syndrome.”  Patients who are anxious about their visits with their doctor often have evidence of increased adrenaline secretion, which typically manifests as anxiety, sweating, a rapid pulse, and elevated blood pressure.  In most cases, after the patient has become more comfortable with their physician, these signs of an overactive sympathetic nervous system begin to subside.  I often see this “syndrome,” particularly in patients seeing me for the first time, or in those who have returned to see me for results of biopsies and other surgeries.  Since I am exclusively a cancer physician and surgeon, the stakes for most of the patients who I see are very high, and many of them are, understandably, very anxious about both the reasons for their visit with me and the potential outcomes of their visit.  I, and many other physicians, have also noted that patients with minimal or very mild baseline hypertension often experience significant “White Coat Syndrome,” particularly with respect to their blood pressure readings at the beginning of their visits with us. 

A newly published clinical study, in the European Journal of Internal Medicine, looks more closely at the relationship between “White Coat Syndrome” and the presence or absence of cardiovascular disease.  In this study, 100 patients already suspected of having coronary artery disease (but never diagnosed) underwent blood pressure measurements, for 24 hours, in an ambulatory clinic, and then underwent ultrasound evaluation of their hearts and carotid arteries (the large arteries in the neck the supply the majority of the blood flow to the brain).  Additionally, these patients also underwent coronary artery angiograms to further assess their coronary arteries. 

This study determined that the patients who presented with “White Coat Syndrome” in the ambulatory clinic were significantly more likely to have coronary artery disease than those patients who, despite already being suspected of having coronary artery disease, presented with normal blood pressure measurements.  Likewise, in the group of patients who initially presented with elevated blood pressure readings, the incidence of abnormal heart function and narrowed carotid arteries (from atherosclerosis) was significantly greater than was observed in the patients who did not initially present with high blood pressure readings. 

In summary, among 100 patients suspected of having coronary artery disease, those who presented initially with elevated blood pressure readings were much more likely to have significant coronary artery disease, abnormal heart function, and narrowed carotid arteries than those patients who presented, initially, with normal blood pressure readings.  Based upon the results of this study, the presence of “White Coat Syndrome” may, at least in some patients, be a harbinger of underlying cardiovascular disease, in addition to being a manifestation of patient anxiety during their visit with their doctor.

 

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:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at:  rwascher@doctorwascher.net

http://www.doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

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Colorectal cancer is the second most common cause of cancer-related death in the United States.  In 2008, an estimated 150,000 new cases of cancer of the colon and rectum will be diagnosed, and nearly 50,000 deaths from this disease are expected to occur.   As I have mentioned in previous columns, colon and rectal cancers can, in most cases, be prevented or, at least, detected at a very early stage, simply by adhering to standard colorectal cancer screening guidelines (please see my 1/7/2008 column for a more detailed discussion of current colorectal cancer screening guidelines).  Currently, colonoscopy, using a video camera mounted at the tip of a long flexible tube (endoscope), remains the gold standard for the detection of premalignant polyps (also called adenomas) in the colon and rectum.  

While the majority of colon and rectal cancers that develop spontaneously appear to arise from premalignant polyps, which resemble fleshy protrusions sprouting from the lining of the large bowel, cancer has also been reported, much less commonly, to arise from lesions that have a flat shape, or even a slightly depressed appearance, with respect to the surrounding layer of tissue that forms the inner lining of the colon and rectum (the mucosa).   These less common forms of premalignant colorectal lesions, often referred to as nonpolypoid colorectal neoplasms (NP-CRNs), were first  widely reported in the Japanese medical literature, but were thought to occur only very rarely in western populations.  A new research paper in the Journal of the American Medical Association, however, suggests that NP-CRNs may not be all that uncommon in the United States after all. 

This new study, which included more than 1,800 patients, assessed the results from elective colonoscopy performed at a large Veterans Administration medical center in 2003 and 2004.  Far from being rare, NP-CRNs were found in nearly 10% of the colonoscopies performed.  The patients were then broken down into three subgroups for further analysis.  Among patients undergoing colonoscopy for routine screening purposes, NP-CRNs were observed 5.8% of patients.  Patients undergoing colonoscopy because of concerning symptoms (such as rectal bleeding, a change in bowel habits, or other gastrointestinal symptoms) were noted to have NP-CRNs in 6% of case.  Among those patients undergoing colonoscopy because of a prior history of colorectal cancer, NP-CRNs were observed in more than 15% of patients, or 1 in every 6 or 7 patients previously treated for colorectal cancer. 

When the results of biopsies taken from these NP-CRNs were assessed, more bad news resulted.  Although fewer than 1% of all patients (and only 0.3% of the screening colonoscopy group patients) were discovered to have early cancerous changes within a NP-CRN lesion, a comparison between NP-CRNs and the more common colorectal polyps revealed a disturbing finding.  Among all 3 subgroups of patients, the presence of early cancers within flat or depressed NP-CRNs occurred nearly 10 times as frequently as was seen in colorectal polyps.  When looking at specific subgroups of patients, once again, this study revealed that in patients undergoing colonoscopy for routine screening purposes, NP-CRNs were 2 times as likely to harbor small cancers when compared to colorectal polyps.  In those patients undergoing colonoscopy for surveillance purposes, because they had previously been diagnosed with colorectal cancer, NP-CRNs, when identified, were almost 64 times more likely to harbor early cancers when compared to polypoid masses!  When comparing the flat type of NP-CRNs with the depressed type, the depressed lesions were most likely to contain cancer (33% of the depressed lesions already had cancer cells present in them).  These worrisome findings are all the more concerning given that, on average, the NP-CRNs containing cancer tended to be considerably smaller than the polyps also found to have cancer present in them (1.6 centimeters in diameter vs. 1.9 centimeters, respectively). 

The findings of this study raise several important new considerations with respect to colorectal cancer screening strategies.  First of all, despite the previous belief that NP-CRNs were rare lesions within western populations, this study suggests that, in fact, they are rather common, at least in a selected group of veterans (on average, veterans tend to have a greater incidence of risk factors associated with colorectal cancer than the general population).   

The finding that, irrespective of the size of the lesions, that NP-CRNs are more likely to harbor small cancerous tumors suggests that the biology of these flat or depressed lesions may be different than that of the more typical, and more common, polypoid lesions.  In this study, a special colored dye was used to stain the lining of the colon and rectum, which made it easier to detect NP-CRNs.  However, this technique is not generally used in routine colonoscopy at most endoscopy centers, and the results of this study, therefore, raise the issue as to whether or not this technique should be routinely added to the current practice of colonoscopy.  Also, even with special staining of the mucosa, NP-CRNs are still more difficult to identify than polypoid lesions, and the borders, or margins, of these flat or slightly depressed lesions are less distinct than is the case for polyps.   

The current data in the medical literature suggests that approximately 10% of polyps may be missed, even by experienced examiners, during routine colonoscopy.  Given the greater difficulty of identifying NP-CRNs during colonoscopy, one can assume that considerably more than 10% of NP-CRNs are currently being missed with even the most thorough conventional colonoscopic examinations.  As NP-CRNs now appear to be significantly more likely to contain small cancers than are polyps, better and more specialized methods of colonoscopy may be necessary to reduce the chance that an early cancer within a small NP-CRN might be missed (and, for the record, virtual CT colonoscopy, which I have discussed previously in another column, cannot currently detect NP-CRNs).  In addition to the greater challenge of detecting NP-CRNs, when compared to colorectal polyps, NP-CRNs that are identified during colonoscopy, and are amenable to removal with the colonoscope, may be more likely to be incompletely removed when compared to polyps.   

Finally, due to declining reimbursements for colonoscopy, gastroenterologists often feel pressured to perform colonoscopy more rapidly than in the past, in order to increase their productivity.  It has been well demonstrated that the more rapidly a colonoscopy is performed, the greater the likelihood that colorectal polyps will be missed.  Since we know that NP-CRNs are considerably more difficult to detect than polyps, the implications of performing rapid colonoscopy are very clear: more NP-CRNs will be missed, even with the addition of new techniques such as mucosal staining, as GI doctors try to perform more colonoscopies per day to keep pace with declining reimbursements for their professional services. 

Because of the many questions that this study has raised, I predict that it will eventually be viewed as a landmark cancer research paper, and its findings will stimulate a serious review of all of our current colorectal cancer screening guidelines.  Currently, it is not clear if the general public is at the same high risk of having NP-CRNs in their colon and rectum (or the same risk of harboring colorectal cancer within NP-CRNs) as this selected population of veterans.  But the provocative findings of this study will, nonetheless, have major implications on future colorectal cancer screening strategies for all of us.  

HEALTH RISKS AFTER STOPPING HORMONE REPLACEMENT THERAPY (HRT) 

I have written about the various findings published, over the past 6 years, from the landmark Women’s Health Initiative (WHI) study in previous columns.  A new update, published this week in the Journal of the American Medical Association, sheds additional light on the long-term health implications of combination hormone replacement therapy (HRT), as taken by millions of women in this country, over the past 5 decades, for the symptoms of menopause.  As I have mentioned before, the use of combination HRT has unequivocally been linked to an increase in the incidence of breast cancer, coronary artery disease (including heart attack), and stroke, among other serious illnesses.  This new WHI study update takes a look at those women who stopped taking HRT when the WHI released its disturbing preliminary findings (and which resulted in the early termination of the WHI combination HRT research trial) in 2002.  In this update, the health status of women who had stopped taking HRT medications for an average of 3 years is reviewed and analyzed.  The results paint a mixed picture of health risks present even 3 years after cessation of HRT. 

A total of 15,730 postmenopausal women were included in this analysis, and consisted of women who took combination HRT pills during the WHI study and women who took placebo (sugar) pills that appeared identical to the HRT pills.  When the data was analyzed, the good news was that, at an average of 3 years after stopping HRT, the risk of coronary artery disease between the two groups of women had, once again, become equal.  That is to say, the increased risk of coronary artery disease that was observed, during the WHI study, among the women randomized to receive HRT had declined to the same levels observed in the group of women who had received only placebo pills.  However, unfortunately, the increased risk of developing cancer persisted in the group of women who had previously taken HRT pills during the study. 

The overall cancer risk among the women who had previously taken HRT pills was 24% greater than for those women who had received placebo pills, although the total numbers of patients diagnosed with new cancers was still small (1.56% of women in the HRT group vs. 1.26% in the placebo group).  In terms of breast cancer risk, specifically, there was a 27% increase in risk among the women who had previously been assigned to receive HRT pills, when compared to the placebo group although, once again, the absolute numbers were rather small in both groups (0.42% vs. 0.33%, respectively).  While a “modest trend” towards decreasing breast cancer risk was observed, over time, among the women in the HRT group, even at 3 years, a significant increase in both the incidence of cancer and the risk of death (from any cause) was still present when compared to the placebo group of women.  When the WHI study data was reanalyzed, 3 years after the women in the HRT group had stopped using HRT, the results indicated a persistent imbalance between the risks and benefits of combination HRT, with a calculated 12% increased risk-to-benefit ratio favoring risk over benefit. 

To summarize this important WHI study update, the incidence of coronary artery disease associated with an average of 5.6 years of HRT use had, by the third year of HRT abstinence, returned to the level observed in age-matched women who had never taken HRT.  However, the risk of cancer, and breast cancer specifically, continued to be elevated, even 3 years after discontinuing HRT, among the women randomized to receive combination HRT pills during the WHI study.   

Longer follow-up of the women assigned to receive HRT pills during this study will have to occur before we can learn when, if ever, the increased risk of cancer (and the overall increased risk of death from all causes) will return to the same levels as has been observed in women who never received HRT.  Once again, my advice to women passing through menopause is that they avoid HRT if at all possible.  For the couple of percent of women who have truly debilitating menopause-associated symptoms that do no respond to non-hormonal treatment, taking the smallest dose of HRT medications, and for the shortest possible duration of time, appears prudent.  

TELEVISION, CHILDREN & OBESITY 

By now, most of us know that increasing amounts of time spent in front of the television have been associated with increasing levels of obesity in children.  Now, a new randomized research study, just published in the Archives of Pediatric & Adolescent Medicine, sheds new light on this topic.   

In this clinical study, 70 overweight children, ages 4 to 7, were randomized to two groups.  In the intervention group, television and computer usage was restricted, while in the control group, no restrictions were implemented.  All of the children participating in this study were evaluated every 6 months throughout the 2-year study. Weight, height, body mass index (BMI), television and computer viewing habits, calorie intake and levels of physical activity were specifically assessed at these 6-month intervals. 

In this small but innovative study, the children in the intervention group showed significant reductions in overall sedentary behavior, with increased physical activity and decreased calorie intake, when compared to the kids in the control group.  When the researchers looked at socioeconomic status as a factor, they found that the children in the lower socioeconomic groups appeared to benefit to a greater degree from restrictions in television and computer usage than did the children in higher socioeconomic groups.  Finally, when analyzing the data, the researchers noted that restricting TV viewing and computer usage resulted in improvements in the BMI of the kids in the intervention group, and that these improvements in the level of obesity were mediated primarily through decreased caloric intake, and not due to the increased level of physical activity also observed in this group.   

In summary, this small randomized study showed that restricting the amount of time that overweight kids spent in front of a television and computer appeared to aid in weight loss, and that this benefit appeared to be primarily related to these children grazing on fewer calories while engaged in these sedentary activities.  If your young children are like mine, weaning them from prolonged exposure to the mesmerizing effects of the hundreds of cable shows available on television is a huge challenge, but a necessary one. 

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html 

Send your feedback to Dr. Wascher at rwascher@doctorwascher.net
 

http://doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

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