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Before Prostate Surgery, Consider ‘Active Surveillance’

Not to be confused with “watchful waiting,” active surveillance is not a do-nothing approach.

Alternatives to the common PSA Test are now being considered. (Source - National Cancer Institute)

Howard Wolinsky is a medical journalist in Flossmoor, Ill., who knows better than to go forward with potentially life-changing surgery without first seeking a second opinion.

Nine years ago, at age 63, when a PSA blood test followed by a biopsy revealed cancer in his prostate gland, the diagnosing urologist said he could operate to remove the offending organ the following week.

Not so fast, Mr. Wolinsky thought, knowing this was not a minor operation that often left men temporarily or permanently impotent, incontinent or both. So, before going under the knife, he consulted Dr. Scott Eggener, a University of Chicago urologist, who reviewed the test results and proposed an alternative strategy called active surveillance.

Not to be confused with “watchful waiting,” active surveillance is not a do-nothing approach. Rather, patients are routinely monitored and referred for surgery or radiation therapy only if their cancer begins to grow or show molecular signs of aggression.

Current estimates are that about half of men found to have prostate cancer could avoid radical treatment and its potential side effects if they were willing to live with having a cancer, albeit a seemingly benign one, in their bodies. These are men whose cancer is deemed, based on its biological characteristics, to be low-risk of progressing to a potentially life-threatening state.


Only if periodic exams reveal that a man’s cancer is shown to be progressing to a more aggressive state would more radical treatment be considered. Within a decade, this generally affects about 5 percent of men who choose active surveillance, Dr. Eggener told me.

Other reasons for abandoning active surveillance and undergoing radical treatment include the patients’ growing anxiety about living with cancer and pressure from family members, and sometimes even from their doctors, to “get it out,” clinicians report.

Watchful waiting, which involves little or no monitoring, is still sometimes suggested but mainly reserved for men with a limited life expectancy for other reasons or those whose health status makes surgery inadvisable.

Based on his PSA of less than 4 and a Gleason score of 6, Mr. Wolinsky said, “Dr. Eggener told me ‘You’re the perfect candidate — the poster child for active surveillance.’” The Gleason score is a measure of the cancer’s aggressiveness, and a composite score of less than 7 is generally deemed low-risk disease.

So starting in 2010 Mr. Wolinsky had a PSA test and digital rectal exam every six months and an annual biopsy of the prostate, which was eventually lengthened to every three years. It’s now been four years since the last biopsy and chances are, unless a worrisome rise in the PSA occurs and other tests indicate an aggressive cancer, he may never need another.

Given the now rapidly changing methods of monitoring and diagnosing the lethality of prostate cancer, it behooves every man told he has cancer in this gland to explore the most currently available management options before deciding on treatment. There are now even support groups to help reassure men with a low-risk cancer who choose active surveillance.

“The field is on fire,” said Dr. Laurence Klotz, a leading expert on urological cancer and pioneer of active surveillance. “Within a few years, we’ll have urine and blood tests that are so reliable we’ll know which men don’t even need a biopsy. Instead of a biopsy, there are now at least five biomarkers and more being developed that can be used as an initial test.”

Even the process of biopsy has changed. For decades, when a possible cancer was suspected based on the PSA test or digital rectal exam, doctors blindly took 12 core samples from the prostate to search for a malignancy. Now an M.R.I. can be done first and a biopsy performed only if and when a potentially serious lesion is revealed. High-resolution ultrasound may even become a simpler and less expensive alternative to an M.R.I., Dr. Klotz said.

To avoid the need for a biopsy altogether, Dr. Klotz is leading a large Canadian clinical trial, called Precise, to determine if an M.R.I. is sufficiently accurate in detecting dangerous cancers and distinguishing them from harmless ones. He estimates, based on early data, that as many as 250,000 men a year in Canada and the United States could avoid unnecessary biopsies without compromising the ability to identify clinically significant cancers.

This approach results in the diagnosis of many fewer indolent cancers that would likely never threaten a man’s life, said Dr. Klotz, a professor of surgery at the University of Toronto and a mentor in the field of prostate cancer diagnosis. “With an M.R.I. we find fewer of these low-grade cancers, and fewer men will be overtreated,” he said.

If Dr. Eggener had his way, he would not even call it cancer for men who are given a Gleason score of 6 or lower, because “it fails to meet the clinical definition of cancer: the ability to cause symptoms, metastasize or lead to death,” he wrote in an email. “Removing the cancer label has been done in other cancers, most notably a subtype of thyroid and bladder cancers. I predict this will eventually happen for Gleason 6 prostate cancer, and in my opinion will be reason for celebration.”

As he has reported, “A high proportion of screen-detected cancers are Gleason 6, and their metastatic potential is negligible.” On biopsy, a cancer may contain cells with different Gleason grades, most commonly a mix of 3 and 4, and the total score adds together the most common ones found in order of their frequency. A pattern 3 has no ability to metastasize, but a 4 is aggressive, Dr. Klotz explained. Thus, a Gleason score of 3 plus 4 is considered less aggressive than 4 plus 3.

There are now genetic tests under study that could help identify the occasional prostate cancers with a low Gleason score that “are bad actors,” Dr. Klotz said. And Dr. Brian Helfand of NorthShore University HealthSystem in Evanston, Ill., and colleagues are studying genetic tests based on more than 100 variants of DNA that may enable men with a high PSA to skip biopsy altogether. At a meeting of the American Urological Association, European researchers described six proteins in the blood that can serve as biomarkers to identify men with an elevated PSA who can safely avoid a biopsy. Of 474 men in their study, 60 percent of the negative biopsies could have been avoided, they reported.

via – NYTimes | Source – NYTimes | Search  》Cancer Research Tests

This Simple Math Problem Supposedly Almost Fooled Einstein Himself

The famous physicist was very nearly defeated by this question from Max Wertheimer.

How a math equation almost fooled Albert Einstein himself!

In 1934, psychologist Max Wertheimer sent a letter to his friend, the physicist Albert Einstein, with the following puzzle enclosed.

There’s an old car that needs to go up and down a hill. The hill is 1 mile going up, and 1 mile going down . Because the car is old, it can only average a speed of 15 mph during the ascent, but may be able to go faster during the descent.

The question is: how fast must the car be going downhill, in order for its speed to reach an average of 30 mph for the entire 2-mile journey?

At the time Einstein received the letter, he had already been honored with the Nobel Prize for Physics, and come up with his famous E = mc2 equation. So this should have been super simple for him to figure out, right? Apparently not. According to German psychologist Gerd Gigerenzer’s book Risk Savvy: How to Make Good Decisions, Einstein wrote that he didn’t see the “trick” until he had already calculated the answer.

This Simple Riddle Almost Fooled Einstein - How To Solve It
Watch this video on YouTube.

YouTuber Presh Talwalkar breaks down the solution to the puzzle in a video, starting by working backwards, and calculating what is the necessary time for a car to average 30 mph on a 2-mile journey. By dividing the journey length, 2, by the speed, 30, you get the time: 1/15 of an hour, or 4 minutes.

Next, Talwalkar figures out how long the car takes going up the hill by dividing the length of that portion of the journey, 1, by its average speed, 15, which simplifies again to 1/15 of an hour, or 4 minutes.

So the car takes 4 minutes to climb the hill, but it must also take 4 minutes for the entirety of the trip, meaning there is no time to get down the other side. The conclusion, then, is that there is no right answer: Wertheimer sent Einstein a trick question.

Coronavirus – There’s a Gender Gap!

Women mount stronger immune responses to infection, scientists say. And in China, men smoke in much greater numbers.


The coronavirus that originated in China has spread fear and anxiety around the world. But while the novel virus has largely spared one vulnerable group — children — it appears to pose a particular threat to middle-aged and older adults, particularly men.

This week, the Chinese Center for Disease Control and Prevention published the largest analysis of coronavirus cases to date. Although men and women have been infected in roughly equal numbers, researchers found, the death rate among men was 2.8 percent, compared with 1.7 percent among women.

Men also were disproportionately affected during the SARS and MERS outbreaks, which were caused by coronaviruses. More women than men were infected by SARS in Hong Kong in 2003, but the death rate among men was 50 percent higher, according to a study published in the Annals of Internal Medicine.

Some 32 percent of men infected with Middle East Respiratory Syndrome died, compared with 25.8 percent of women. Young adult men also died at higher rates than female peers during the influenza epidemic of 1918.

A number of factors may be working against men in the current epidemic, scientists say, including some that are biological, and some that are rooted in lifestyle.

When it comes to mounting an immune response against infections, men are the weaker sex.

“This is a pattern we’ve seen with many viral infections of the respiratory tract — men can have worse outcomes,” said Sabra Klein, a scientist who studies sex differences in viral infections and vaccination responses at the Johns Hopkins Bloomberg School of Public Health.

“We’ve seen this with other viruses. Women fight them off better,” she added.

Women also produce stronger immune responses after vaccinations, and have enhanced memory immune responses, which protect adults from pathogens they were exposed to as children.

“There’s something about the immune system in females that is more exuberant,” said Dr. Janine Clayton, director of the Office of Research on Women’s Health at the National Institutes of Health.

But there’s a high price, she added: Women are far more susceptible to autoimmune diseases, like rheumatoid arthritis and lupus, in which the immune system shifts into overdrive and attacks the body’s own organs and tissues.

Nearly 80 percent of those with autoimmune diseases are women, Dr. Clayton noted.

The reasons women have stronger immune responses aren’t entirely clear, and the research is still at an early stage, experts caution.

One hypothesis is that women’s stronger immune systems confer a survival advantage to their offspring, who imbibe antibodies from mothers’ breast milk that help ward off disease while the infants’ immune systems are still developing.

A stew of biological factors may be responsible, including the female sex hormone estrogen, which appears to play a role in immunity, and the fact that women carry two X chromosomes, which contain immune-related genes. Men, of course, carry only one.

Experiments in which mice were exposed to the SARS coronavirus found that the males were more susceptible to infection than the females, a disparity that increased with age.

The male mice developed SARS at lower viral exposures, had a lower immune response and were slower to clear the virus from their bodies. They suffered more lung damage, and died at higher rates, said Dr. Stanley Perlman, a professor of microbiology at the University of Iowa who was the senior author of the study.

When researchers blocked estrogen in the infected females or removed their ovaries, they were more likely to die, but blocking testosterone in male mice made no difference, indicating that estrogen may play a protective role.

“It’s an exaggerated model of what happens in humans,” Dr. Perlman said. “The differences between men and women are subtle — in mice, it’s not so subtle.”


Health behaviors that differ by sex in some societies may also play a role in disparate responses to infections.

China has the largest population of smokers in the world — 316 million people — accounting for nearly one-third of the world’s smokers and 40 percent of tobacco consumption worldwide. But just over 2 percent of Chinese women smoke, compared with more than half of all men.

Chinese men also have higher rates of Type 2 diabetes and high blood pressure than women, both of which increase the risk of complications following infection with the coronavirus. Rates of chronic obstructive pulmonary disease are almost twice as high among Chinese men as among women.

In the United States, women are more proactive about seeking health care than men, and some small studies have found the generalization applies to Chinese students at universities in the United States, as well.

In unpublished studies, Chinese researchers have emphasized that patients whose diagnoses were delayed, or who had severe pneumonia when they were first diagnosed, were at greatest risk of dying.

One study of 4,021 patients with the coronavirus emphasized the importance of early detection, particularly in older men. And men have been turning up in hospitals with more advanced disease.

But in areas of China outside Hubei Province, the disease’s epicenter and where the majority of those affected are concentrated, the patterns are different: The disease appears to have dramatically lower mortality rates, and men are being infected at much higher rates than women, according to the Chinese C.D.C. analysis.

Men may have a “false sense of security” when it comes to the coronavirus, said Akiko Iwasaki, a professor of immunology at Yale University who studies why some viruses affect women more severely.

Gathering and analyzing data about the new virus by sex is important both for the scientists studying it and for the general public, experts said.

Since the start of the outbreak, for example, public health officials have emphasized the importance of washing hands well and often, to prevent infection. But several studies have found that men — even health care workers — are less likely to wash their hands or to use soap than women, Dr. Klein said.

“We make these broad sweeping assumptions that men and women are the same behaviorally, in terms of comorbidities, biology and our immune system, and we just are not,” Dr. Klein said.

via – NYTimes