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Abnormal results on a prostate-specific antigen (PSA) screening test for cancer are typically followed by a systematic biopsy. During that procedure, doctors use a long needle to extract roughly a dozen samples from the prostate while looking at the gland on an ultrasound machine. Those samples can then be checked for cancer under a microscope.

Limitations and concerns

But systematic biopsies can be problematic. A major concern is that they overdiagnose low-grade, slow-growing tumors that might never become life-threatening, thereby leading to unnecessary treatments.

Researchers are seeking alternatives to the systematic biopsy in men flagged by PSA screening. One option is to start with a magnetic resonance imaging (MRI) scan of the prostate, and then focus the biopsy only on areas that look suspicious for cancer. This is called an MRI-targeted biopsy, and it’s becoming increasingly common.

Could an MRI miss early-stage cancer that later turns out to be incurable? This is an outstanding worry, especially since systematic biopsies sometimes find newly-forming cancer that MRIs aren’t yet able to detect. Indeed, systematic and targeted biopsies are often given together to boost the odds of finding clinically significant disease that may need immediate treatment.

Methodology

Now, a large Swedish study provides encouraging evidence favoring the MRI-only approach.

The team invited 38,316 men ranging from 50 to 60 years in age to undergo PSA screening. If a man’s PSA level was 3.0 nanograms per milliliter (ng/mL) or higher, then he was enrolled into the study. The investigators wound up with 13,153 men who were randomly distributed between two groups:

• Systematic biopsy group: All the men in this group got a systematic biopsy plus an MRI. If a man’s MRI was positive for suspicious lesions, then he also got a targeted biopsy.
• MRI-targeted biopsy group: All of the men in this group got an MRI, but none got a systematic biopsy. Men with suspicious lesions on MRI got a targeted biopsy.

This initial screening round was followed by repeat screening rounds — all following the same protocols — at two-, four-, and eight-year-intervals.

What the study showed

After a median follow-up of 3.9 years (starting from and including the first screening round), prostate cancer had been detected in 185 men from the MRI-targeted group and 298 men from the systematic biopsy group. Systematic biopsies generated more clinically insignificant cancer diagnoses — 159 compared to 68 in the MRI-targeted group. During the first screening round, “The risk of such a diagnosis was 51% lower in the MRI-targeted biopsy group than the systematic biopsy group,” the authors wrote.

The authors emphasized that omitting biopsies in patients with MRI-negative results cut diagnoses of clinically insignificant cancer, meaning cancer that is slow-growing and may never need treatment, by more than half. “And importantly, the associated risk of detecting clinically significant cancer during follow-up and at later screening visits was very low in both groups,” said Dr. Jonas Hugosson, chief urologist at the University of Gothenberg and the study’s first author. “A total of 14 such cases (0.2 % of men who participated) were diagnosed in the systematic biopsy group and eight (0.1 %) in the MRI-targeted biopsy group.”

Commentary from experts

“This study provides encouraging — though very early — data that supports the increasing use of MRI as the first diagnostic modality, following evaluation of an abnormal PSA value,” said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor-in-chief of the Harvard Medical School Guide to Prostate Diseases. “The practice of not automatically going to prostate needle biopsy when an abnormal PSA is detected has gained in popularity in Europe, and this study may help increase its usefulness in the United States.”

“While these results are encouraging, the decision to omit biopsy in men with a negative MRI must be individualized based on the risk of detecting prostate cancer,” added Dr. Boris Gershman, a urologist at Beth Israel Deaconess Medical Center and an assistant professor at Harvard Medical School focusing on prostate and bladder cancer. “For example, biopsy may still be considered in men with markedly elevated PSA, even if the prostate MRI does not identify any lesions.”

About the Author

Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases

Charlie Schmidt is an award-winning freelance science writer based in Portland, Maine. In addition to writing for Harvard Health Publishing, Charlie has written for Science magazine, the Journal of the National Cancer Institute, Environmental Health Perspectives, … See Full Bio View all posts by Charlie Schmidt

About the Reviewer

Marc B. Garnick, MD, Editor in Chief, Harvard Medical School Annual Report on Prostate Diseases; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Marc B. Garnick is an internationally renowned expert in medical oncology and urologic cancer. A clinical professor of medicine at Harvard Medical School, he also maintains an active clinical practice at Beth Israel Deaconess Medical … See Full Bio View all posts by Marc B. Garnick, MD

Celiac disease is a digestive and immune disorder that can keep the body from absorbing necessary nutrients. “Our conception and awareness of celiac disease has evolved over the past few decades, but there are still aspects that remain poorly understood,” says Dr. Ciaran Kelly, medical director of the Celiac Center at Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School.

Perhaps not surprisingly, misconceptions are widespread among the general public. One example? Many people assume that everyone who has celiac disease is plagued by abdominal pain, bloating, or diarrhea. But actually, many adults newly diagnosed with this inherited gluten intolerance don’t have these symptoms.

What’s more, gluten — the sticky protein found in grains such as wheat, barley, and rye — can cause gastrointestinal distress and other symptoms in people who don’t have celiac disease. Read on for a deeper dive into four myths and facts about celiac disease and related digestive conditions.

Myth # 1: Celiac disease is usually diagnosed at a young age

Not typically. While celiac disease can develop any time after a baby’s first exposure to gluten, it’s usually diagnosed much later in life. According to the National Celiac Association, the average age of diagnosis is between 46 and 56. Around 25% of people are diagnosed after age 60.

Celiac disease is slightly more common in women and among people with other autoimmune conditions, including type 1 diabetes, Hashimoto’s thyroiditis (a common cause of low thyroid levels), and dermatitis herpetiformis (a rare condition marked by an itchy, blistering rash).

“We don’t know why some people go from being susceptible to actually having celiac disease,” says Dr. Kelly. The prevailing theory is that some sort of physical or emotional stress — such as a viral infection, surgery, or anxiety from a stressful life event — may “flip the switch” and cause the disease to appear, he says. “Increasing numbers of people are being diagnosed at midlife and older, often after they’re found to have conditions such as anemia or osteoporosis caused by nutrient deficiencies,” says Dr. Kelly.

Myth #2: Celiac disease only affects the gut

When people have celiac disease, eating gluten triggers an immune system attack that can ravage the lining of the small intestine. A healthy small intestine is lined with fingerlike projections, called villi, that absorb nutrients. In celiac disease, the immune system attacks the villi, causing them to flatten and become inflamed — and thus unable to adequately absorb nutrients.

While gastrointestinal problems can occur, they aren’t always present. In fact, celiac disease can present with many different symptoms that affect the nervous, endocrine, and skeletal systems. A few examples are brain fog, changes in menstrual periods, or muscle and joint pain.

Myth # 3: Celiac disease versus gluten intolerance

If you feel sick after eating gluten, you probably have celiac disease, right? Actually, that may not be true. Some people have non-celiac gluten sensitivity (also called gluten intolerance), which can cause uncomfortable digestive symptoms after eating gluten. But gluten intolerance differs from celiac disease.

• Celiac disease is diagnosed with blood tests that look for specific antibodies. If antibodies are present, a definitive diagnosis requires an intestinal biopsy to look for signs of damage that characterize the condition.
• Non-celiac gluten sensitivity does not trigger antibodies or cause intestinal damage. Yet some people with this problem say they also experience brain fog, trouble concentrating, muscle aches and pain, and fatigue after eating gluten-containing foods.

“Non-celiac gluten sensitivity appears to be a real phenomenon, but it’s not well defined,” says Dr. Kelly. It’s unclear whether people experiencing it are intolerant to gluten or to something else in gluten-containing foods.

• One possibility is sugarlike molecules known as FODMAPs, which are found in many foods — including wheat. Short for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, gas and bloating can occur when gut bacteria feed on FODMAPs.
• Another possibility is an allergy to wheat, which can cause symptoms such as swelling, itching, or irritation of the mouth and throat after eating wheat. Other symptoms include a skin rash, stuffy nose, and headache, as well as cramps, nausea, and vomiting. Some people may develop a life-threating allergic reaction known as anaphylaxis.

Myth #4: A gluten-free diet always relieves the symptoms and signs of celiac disease

The sole treatment for celiac disease — adopting a diet that avoids all gluten-containing foods — doesn’t always help. This problem is known as nonresponsive celiac disease.

“About 20% of people with celiac disease have ongoing symptoms, despite their best efforts to stick to a gluten-free diet,” says Dr. Kelly. Others have intermittent signs and symptoms, particularly when they are accidentally exposed to gluten. Accidental exposures often happen when people eat prepared or restaurant foods that claim to be gluten-free but are not. Cross contamination with gluten-containing foods is another potential route.

Potential solutions to nonresponsive celiac disease are being studied. Three promising approaches are:

• Enzymes that break down gluten, which people could take alongside gluten-containing foods. “It’s a similar concept to the lactase pills taken by people who are lactose intolerant to help them digest dairy products,” says Dr. Kelly.
• Dampening the immune response to gluten by inhibiting an enzyme called tissue transglutaminase that makes gluten more potent as an antigen.
• Reprogramming the immune response to prevent the body from reacting to gluten.

About the Author

Julie Corliss, Executive Editor, Harvard Heart Letter

Julie Corliss is the executive editor of the Harvard Heart Letter. Before working at Harvard, she was a medical writer and editor at HealthNews, a consumer newsletter affiliated with The New England Journal of Medicine. She … See Full Bio View all posts by Julie Corliss

About the Reviewer

Howard E. LeWine, MD, Chief Medical Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Howard LeWine is a practicing internist at Brigham and Women’s Hospital in Boston, Chief Medical Editor at Harvard Health Publishing, and editor in chief of Harvard Men’s Health Watch. See Full Bio View all posts by Howard E. LeWine, MD