Animal Study Finds Tiny Dose of Sildenafil (Viagra) May Reduce Colon Cancer Risk

MedicalResearch.com Interview with:

Darren D. Browning, PhD | Professor Department of Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University Georgia Cancer Center, Augusta, Georgia 30912-2100

Dr. Darren Browning

Darren D. Browning, PhD | Professor
Department of Biochemistry and Molecular Biology,
Medical College of Georgia at Augusta University
Georgia Cancer Center,
Augusta, Georgia 30912-2100

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cancer of the colon and rectum is one of the most commonly diagnosed and has a high mortality because it is often identified at an advanced stage. In the United States the average overall risk of having to deal with this disease at some point is around one in twenty-five, but the risk is much higher for people who have previously had polyps removed or if a close relative was diagnosed with colon cancer. The risk is even higher for patients with inflammatory bowel disease or heritable disorders such as familial adenomatous polyposis and lynch syndrome. While chemoprevention is clearly warranted, there are currently no drugs available that can reduce the risk for those predisposed to colorectal cancer.

Previous work from our laboratory has shown that drugs like sildenafil that inhibit phosphodiesterase 5 (PDE5), have a profound effect on the epithelial lining of the intestine. Our recent work has shown that these drugs can prevent intestinal cancers in two different mouse models of human disease. While this class of drugs is best known for treating erectile dysfunction, due to a low side-effect profile they are also prescribed for long-term daily use to treat pulmonary arterial hypertension (PAH) and benign prostate hyperplasia

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Obesity and Colon Polyp Risk

Jenifer I Fenton Assistant Professor Department of Food Science and Human Nutrition Michigan State University East Lansing, MI 48824MedicalResearch.com Interview with:
Jenifer I Fenton
Assistant Professor
Department of Food Science and Human Nutrition
Michigan State University
East Lansing, MI 48824

MedicalResearch.com: What are the main findings of the study?

Dr. Fenton: This was a cross-sectional study, and thus, a snapshot in time. Although it cannot infer cause or temporality of obesity and colon polyp risk in men, it does show that obese men were more likely to have a polyp than their lean counterpart. In addition, there were serum biomarkers also associated with this risk. This could eventually lead to future blood tests to identify individuals at greater risk for polyps and inform screening recommendations.
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Study: Virtual colonoscopy without laxative equals standard in identifying clinically significant polyps

Computed tomographic colonography (CTC), also known as virtual colonoscopy, administered without laxatives is as accurate as conventional colonoscopy in detecting clinically significant, potentially cancerous polyps, according to a study performed jointly at the San Francisco VA Medical Center, the University of California, San Francisco and Massachusetts General Hospital.

“I think we have demonstrated that laxative-free CTC is a valid tool for detecting polyps that are clinically significant,” said co-author and site principal investigator Judy Yee, MD, chief of radiology at SFVAMC and professor and vice chair of radiology at UCSF.

The study was published in the May 15 issue of Annals of Internal Medicine.

Virtual colonoscopy, which has been approved by the American Cancer Society as a valid screening test for colorectal cancer, uses a CT scanner to screen for cancers and polyps in the colon non-invasively. In standard optical colonoscopy (OC), a physician inserts a six-foot-long scope into the entire colon. Currently, both methods call for patients to take a bowel-cleansing laxative before the procedure.

With laxative-free CTC, explained Yee, patients do not have to go through bowel cleansing before the exam, but instead begin a low fiber diet two days before the test. They also ingest a tagging agent the day before the exam, which mixes with residual material in the colon and can then be identified and removed digitally when radiologists interpret the scans.

“The use of laxatives is often viewed as the worse aspect of having not only a virtual colonoscopy but an optical colonoscopy,” said Yee, who has pioneered the use of virtual colonoscopy within the VA health care system and at UCSF. “I hope that this research will encourage patients who have delayed screening for colon cancer to be examined with this less invasive method.”

The study of 605 patients, aged 50 to 85, assessed the accuracy of laxative-free CTC in detecting lesions 6 millimeters or larger in size compared with standard optical colonoscopy.

The authors found that laxative-free CTC exams detected clinically significant polyps 10 mm or larger with 91 percent accuracy compared to OC exams, which were 95 percent accurate. Statistically, there is no difference between these two numbers, said Yee.

Scan sensitivity using laxative-free CT colonography decreases with polyp size, as it does for regular CT colonography, she said. With polyps measuring 6 mm, sensitivity for CTC was 59 percent, compared with standard colonoscopy at 76 percent.

The smaller the polyp, the less likely it is to harbor malignancy. For diminutive polyps 5 mm or less, there is an extremely low risk of cancer, and these polyps may not need to be removed.

For polyps between 6 and 9 mm in size, the decision about whether to remove them depends on the patient’s risk factors and how many are found, said Yee.

“Polyps 10 millimeters or larger unquestionably come out,” she said.

During the study, three of the 605 subjects were found to have cancerous polyps. The cancers were identified by both the laxative-free virtual colonoscopy and the standard OC exam.

The researchers also surveyed the research participants about their experiences while preparing for the examinations. They found that laxative-free virtual colonoscopy scored higher on all survey questions, and was indicated by more participants to be their exam type of choice.

Yee noted that the current study is one of the first and largest to measure the effectiveness of the new, laxative-free procedure. Because the procedure is still in the early stages of development, additional studies still need to be conducted, she said.

She predicts that once radiologists are trained in reading the new images and gain experience with the exam process, laxative-free CTC exams will be available wherever virtual colonoscopies are performed.

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Co-authors of the study are Michael E. Zalis, MD, Michael A. Blake, MB, BCh, Wenli Cai, PhD, Peter F. Hahn, MD, PhD, Elkan F. Halpern, PhD, Imarana G. Kazam, PhD, Myles Keroack, MD, Cordula Magee, PhD, Janne J. Nappi, PhD, Rocio Perez-Johnston, MD, Abhinav Vij, MD and Hiroyuki Yoshida, PhD, of Massachusetts General Hospital, and John R. Saltzman, MD, of Brigham and Women’s Hospital, Boston, Massachusetts.

The authors had no conflicts of interest.

The study was supported by funds from GE Healthcare and the American Cancer Society, some of which were administered by the Northern California Institute for Research and Education.

Blacks and Hispanics at Higher Risk for Precancerous Colorectal Polyps

Colonoscopy may be preferable to sigmoidoscopy for these populations

Newswise — New York, NY (May 3, 2012) — Blacks and Hispanics have a significantly higher risk of developing precancerous colorectal polyps compared with whites, according to a study by researchers at NewYork – Presbyterian Hospital/Columbia University Medical Center. The findings appeared in the online edition of Alimentary Pharmacology and Therapeutics.

“Our data suggest that we need to redouble our efforts to increase colon cancer screening in areas with large numbers of racial and ethnic minorities,” said lead author Benjamin Lebwohl, MD, MS, assistant professor of clinical medicine and epidemiology at NewYork – Presbyterian Hospital/Columbia University Medical Center and Columbia University’s Mailman School of Public Health.

The study also found that blacks and Hispanics have a higher risk of developing polyps in the upper portion of the colon, compared with whites. “These lesions would have been missed had these patients undergone sigmoidoscopy, which examines only the lower half of the colon,” said Dr. Lebwohl. “Therefore, colonoscopy, which examines the entire colon, may be preferable to sigmoidoscopy as a screening test for blacks and Hispanics.”

Colorectal cancer caused an estimated 51,370 deaths in 2010 – the last year for which data are available. This type of cancer is largely preventable if caught early, in the form of precancerous polyps, or adenomas. Such polyps are effectively treated with removal during colonoscopy.

The researchers looked at rates of advanced adenomas — polyps 10 mm or larger that exhibited aggressive features under microscopic examination. “These are the kinds of polyps that we are most concerned may eventually develop into cancer,” said Fay Kastrinos, MD, MPH, assistant professor of clinical medicine at NewYork – Presbyterian Hospital/Columbia University Medical Center and senior author of the study. “We found that blacks and Hispanics were roughly twice as likely to have advanced adenomas, compared with whites, after adjusting for factors such as age and family history.”

Previous studies had shown that colorectal cancer incidence and mortality are higher in blacks than in whites, and that blacks are typically younger at the time of diagnosis than are whites. Little was known about the risk of adenomas among Hispanics.

In the current study, the first to compare adenomas in white, blacks, and Hispanics, the investigators analyzed data from 5,075 men and women age 50 or older who underwent first-time colonoscopy at NewYork – Presbyterian Hospital/Columbia University Medical Center from 2006 to 2010. The study population was 70 percent white, 18 percent Hispanic, and 12 percent black, with a mean age of 62. None of the subjects had signs or symptoms of colon cancer at the time of screening. At least one adenoma was detected in 19 percent of whites, 22 percent of Hispanics, and 26 percent of blacks, the researchers reported.

The findings run counter to existing statistics showing that Hispanics have a lower rate of colon cancer compared with whites. “Surprisingly, we found that Hispanics have a slightly higher rate of precancerous polyps,” said Dr. Lebwohl. “This adds to other recent evidence that the rate of colorectal cancer among Hispanics may be increasing with acculturation.”

Doctors generally advise patients to get an initial screening test at age 50, when overall rates of colon cancer begin to increase.

The research paper is titled, “Risk of colorectal adenomas and advanced neoplasia in Hispanic, black and white patients undergoing screening colonoscopy.” The other co-authors are Kristina Capiak and Alfred. I. Neugut, at NewYork – Presbyterian Hospital/Columbia University Medical Center.

This research was supported by the National Center for Research Resources (KL2 RR024157, BL) and the National Cancer Institute (K07 CA151769-01, FK).

Source: Newswise