腰椎間盤突出微創手術

椎間盤突出即脊椎之間的軟骨向後突出，繼而壓着神經線。隨着年紀大，腰椎老化，脊椎的神經管道變小，壓迫神經線，會引致椎管狹窄。患者會有背部或下肢疼痛、麻痹無力，甚至不良於行，影響大小便功能。
症狀輕微的患者可經非手術方法如藥物及復健改善，但若病情嚴重就可能要進行手術。傳統開放性手術須全身麻醉，於背部開刀，切開約4厘米造口，移開肌肉，箝走部份椎板骨，再切除突出的椎間盤。傳統開放性手術缺點是對腰背軟組織，特別是背部肌肉傷害較大，手術後疼痛較大，須住院幾日。
醫院管理局近年引入微創脊椎手術，包括顯微內窺鏡切除術和全內窺鏡切除術。當中全內窺鏡切除術以微創方式，只須在背部開一粒豆大小，約一厘米造口，再將導管伸入，穿梭於脊椎部位肌肉之間，並避開脊椎神經，抵達目標位置切除突出的椎間盤。

適合長者　即日可出院

手術以局部麻醉進行，因手術期間病人要告訴醫生有否感到痛楚麻痹，讓醫生知道導管穿梭體內時有否觸及神經線。德國研究顯示，接受全內窺鏡切除術治療病人，經過約兩年觀察及跟進，發現術後背痛減少，出現手術造成創傷減少，並較快復原。
這種微創脊椎手術適合部份不耐受傳統開刀手術的年長患者，因為手術創傷性較少，可以使用局部麻醉，伸入的導管只撥開周圍肌肉，毋須把肌肉切開，以盡量保留肌肉的功能。
術後疼痛較開放性手術少，所以醫生只須處方較少、較輕的止痛藥便可，病人更可即日下床行走及出院。
微創脊椎手術技術亦能應用於治療脊椎退化、創傷及變形等，亦可紓緩脊椎腫瘤造成痛楚。但是部份病情複雜、脊椎嚴重變形等患者並不適合用微創方法治療。

AN OLD IDEA, REVIVED: STARVE CANCER TO DEATH

In the early 20th century, the German biochemist Otto Warburg believed that tumors could be treated by disrupting their source of energy. Hisidea was dismissed for decades — until now.

The story of modern cancer research begins, somewhat improbably, with the sea urchin. In the first decade of the 20th century, the German biologist Theodor Boveri discovered that if he fertilized sea-urchin eggs with two sperm rather than one, some of the cells would end up with the wrong number of chromosomes and fail to develop properly. It was the era before modern genetics, but Boveri was aware that cancer cells, like the deformed sea urchin cells, had abnormal chromosomes; whatever caused cancer, he surmised, had something to do with chromosomes.

Today Boveri is celebrated for discovering the origins of cancer, but another German scientist, Otto Warburg, was studying sea-urchin eggs around the same time as Boveri. His research, too, was hailed as a major breakthrough in our understanding of cancer. But in the following decades, Warburg’s discovery would largely disappear from the cancer narrative, his contributions considered so negligible that they were left out of textbooks altogether.

Unlike Boveri, Warburg wasn’t interested in the chromosomes of sea-urchin eggs. Rather, Warburg was focused on energy, specifically on how the eggs fueled their growth. By the time Warburg turned his attention from sea-urchin cells to the cells of a rat tumor, in 1923, he knew that sea-urchin eggs increased their oxygen consumption significantly as they grew, so he expected to see a similar need for extra oxygen in the rat tumor. Instead, the cancer cells fueled their growth by swallowing up enormous amounts of glucose (blood sugar) and breaking it down without oxygen. The result made no sense. Oxygen-fueled reactions are a much more efficient way of turning food into energy, and there was plenty of oxygen available for the cancer cells to use. But when Warburg tested additional tumors, including ones from humans, he saw the same effect every time. The cancer cells were ravenous for glucose.

Warburg’s discovery, later named the Warburg effect, is estimated to occur in up to 80 percent of cancers. It is so fundamental to most cancers that a positron emission tomography (PET) scan, which has emerged as an important tool in the staging and diagnosis of cancer, works simply by revealing the places in the body where cells are consuming extra glucose. In many cases, the more glucose a tumor consumes, the worse a patient’s prognosis.

In the years following his breakthrough, Warburg became convinced that the Warburg effect occurs because cells are unable to use oxygen properly and that this damaged respiration is, in effect, the starting point of cancer. Well into the 1950s, this theory — which Warburg believed in until his death in 1970 but never proved — remained an important subject of debate within the field. And then, more quickly than anyone could have anticipated, the debate ended. In 1953, James Watson and Francis Crick pieced together the structure of the DNA molecule and set the stage for the triumph of molecular biology’s gene-centered approach to cancer. In the following decades, scientists came to regard cancer as a disease governed by mutated genes, which drive cells into a state of relentless division and proliferation. The metabolic catalysts that Warburg spent his career analyzing began to be referred to as “housekeeping enzymes” — necessary to keep a cell going but largely irrelevant to the deeper story of cancer.

“It was a stampede,” says Thomas Seyfried, a biologist at Boston College, of the move to molecular biology. “Warburg was dropped like a hot potato.” There was every reason to think that Warburg would remain at best a footnote in the history of cancer research. (As Dominic D’Agostino, an associate professor at the University of South Florida Morsani College of Medicine, told me, “The book that my students have to use for their cancer biology course has no mention of cancer metabolism.”) But over the past decade, and the past five years in particular, something unexpected happened: Those housekeeping enzymes have again become one of the most promising areas of cancer research. Scientists now wonder if metabolism could prove to be the long-sought “Achilles’ heel” of cancer, a common weak point in a disease that manifests itself in so many different forms.

There are typically many mutations in a single cancer. But there are a limited number of ways that the body can produce energy and support rapid growth. Cancer cells rely on these fuels in a way that healthy cells don’t. The hope of scientists at the forefront of the Warburg revival is that they will be able to slow — or even stop — tumors by disrupting one or more of the many chemical reactions a cell uses to proliferate, and, in the process, starve cancer cells of the nutrients they desperately need to grow.

Even James Watson, one of the fathers of molecular biology, is convinced that targeting metabolism is a more promising avenue in current cancer research than gene-centered approaches. At his office at the Cold Spring Harbor Laboratory in Long Island, Watson, 88, sat beneath one of the original sketches of the DNA molecule and told me that locating the genes that cause cancer has been “remarkably unhelpful” — the belief that sequencing your DNA is going to extend your life “a cruel illusion.” If he were going into cancer research today, Watson said, he would study biochemistry rather than molecular biology.

“I never thought, until about two months ago, I’d ever have to learn the Krebs cycle,” he said, referring to the reactions, familiar to most high-school biology students, by which a cell powers itself. “Now I realize I have to.”

Born in 1883 into the illustrious Warburg family, Otto Warburg was raised to be a science prodigy. His father, Emil, was one of Germany’s leading physicists, and many of the world’s greatest physicists and chemists, including Albert Einstein and Max Planck, were friends of the family. (When Warburg enlisted in the military during World War I, Einstein sent him a letter urging him to come home for the sake of science.) Those men had explained the mysteries of the universe with a handful of fundamental laws, and the young Warburg came to believe he could bring that same elegant simplicity and clarity to the workings of life. Long before his death, Warburg was considered perhaps the greatest biochemist of the 20th century, a man whose research was vital to our understanding not only of cancer but also of respiration and photosynthesis. In 1931 he won the Nobel Prize for his work on respiration, and he was considered for the award on two other occasions — each time for a different discovery. Records indicate that he would have won in 1944, had the Nazis not forbidden the acceptance of the Nobel by German citizens.

That Warburg was able to live in Germany and continue his research throughout World War II, despite having Jewish ancestry and most likely being gay, speaks to the German obsession with cancer in the first half of the 20th century. At the time, cancer was more prevalent in Germany than in almost any other nation. According to the Stanford historian Robert Proctor, by the 1920s Germany’s escalating cancer rates had become a “major scandal.” A number of top Nazis, including Hitler, are believed to have harbored a particular dread of the disease; Hitler and Joseph Goebbels took the time to discuss new advances in cancer research in the hours leading up to the Nazi invasion of the Soviet Union. Whether Hitler was personally aware of Warburg’s research is unknown, but one of Warburg’s former colleagues wrote that several sources told him that “Hitler’s entourage” became convinced that “Warburg was the only scientist who offered a serious hope of producing a cure for cancer one day.”

Although many Jewish scientists fled Germany during the 1930s, Warburg chose to remain. According to his biographer, the Nobel Prize-winning biochemist Hans Krebs, who worked in Warburg’s lab, “science was the dominant emotion” of Warburg’s adult life, “virtually subjugating all other emotions.” In Krebs’s telling, Warburg spent years building a small team of specially trained technicians who knew how to run his experiments, and he feared that his mission to defeat cancer would be set back significantly if he had to start over. But after the war, Warburg fired all the technicians, suspecting that they had reported his criticisms of the Third Reich to the Gestapo. Warburg’s reckless decision to stay in Nazi Germany most likely came down to his astonishing ego. (Upon learning he had won the Nobel Prize, Warburg’s response was, “It’s high time.”)

“Modesty was not a virtue of Otto Warburg,” says George Klein, a 90-year-old cancer researcher at the Karolinska Institute in Sweden. As a young man, Klein was asked to send cancer cells to Warburg’s lab. A number of years later, Klein’s boss approached Warburg for a recommendation on Klein’s behalf. “George Klein has made a very important contribution to cancer research,” Warburg wrote. “He has sent me the cells with which I have solved the cancer problem.” Klein also recalls the lecture Warburg gave in Stockholm in 1950 at the 50th anniversary of the Nobel Prize. Warburg drew four diagrams on a blackboard explaining the Warburg effect, and then told the members of the audience that they represented all that they needed to know about the biochemistry of cancer.

Warburg was so monumentally stubborn that he refused to use the word “mitochondria,” even after it had been widely accepted as the name for the tiny structures that power cells. Instead Warburg persisted in calling them “grana,” the term he came up with when he identified those structures as the site of cellular respiration. Few things would have been more upsetting to him than the thought of Nazi thugs chasing him out of the beautiful Berlin institute, modeled after a country manor and built specifically for him. After the war, the Russians approached Warburg and offered to erect a new institute in Moscow. Klein recalls that Warburg told them with great pride that both Hitler and Stalin had failed to move him. As Warburg explained to his sister: “Ich war vor Hitler da” — “I was here before Hitler.”

Imagine two engines, the one being driven by complete and the other by incomplete combustion of coal,” Warburg wrote in 1956, responding to a criticism of his hypothesis that cancer is a problem of energy. “A man who knows nothing at all about engines, their structure and their purpose may discover the difference. He may, for example, smell it.” 

The “complete combustion,” in Warburg’s analogy, is respiration. The “incomplete combustion,” turning nutrients into energy without oxygen, is known as fermentation. Fermentation provides a useful backup when oxygen can’t reach cells quickly enough to keep up with demand. (Our muscle cells turn to fermentation during intense exercise.) Warburg thought that defects prevent cancer cells from being able to use respiration, but scientists now widely agree that this is wrong. A growing tumor can be thought of as a construction site, and as today’s researchers explain it, the Warburg effect opens the gates for more and more trucks to deliver building materials (in the form of glucose molecules) to make “daughter” cells.

If this theory can explain the “why” of the Warburg effect, it still leaves the more pressing question of what, exactly, sets a cell on the path to the Warburg effect and cancer. Scientists at several of the nation’s top cancer hospitals have spearheaded the Warburg revival, in hopes of finding the answer. These researchers, typically molecular biologists by training, have turned to metabolism and the Warburg effect because their own research led each of them to the same conclusion: A number of the cancer-causing genes that have long been known for their role in cell division also regulate cells’ consumption of nutrients.

Craig Thompson, the president and chief executive of the Memorial Sloan Kettering Cancer Center, has been among the most outspoken proponents of this renewed focus on metabolism. In Thompson’s analogy, the Warburg effect can be thought of as a social failure: a breakdown of the nutrient-sharing agreement that single-celled organisms signed when they joined forces to become multicellular organisms. His research showed that cells need to receive instructions from other cells to eat, just as they require instructions from other cells to divide. Thompson hypothesized that if he could identify the mutations that lead a cell to eat more glucose than it should, it would go a long way toward explaining how the Warburg effect and cancer begin. But Thompson’s search for those mutations didn’t lead to an entirely new discovery. Instead, it led him to AKT, a gene already well known to molecular biologists for its role in promoting cell division. Thompson now believes AKT plays an even more fundamental role in metabolism.

The protein created by AKT is part of a chain of signaling proteins that is mutated in up to 80 percent of all cancers. Thompson says that once these proteins go into overdrive, a cell no longer worries about signals from other cells to eat; it instead stuffs itself with glucose. Thompson discovered he could induce the “full Warburg effect” simply by placing an activated AKT protein into a normal cell. When that happens, Thompson says, the cells begin to do what every single-celled organism will do in the presence of food: eat as much as it can and make as many copies of itself as possible. When Thompson presents his research to high-school students, he shows them a slide of mold spreading across a piece of bread. The slide’s heading — “Everyone’s first cancer experiment” — recalls Warburg’s observation that cancer cells will carry out fermentation at almost the same rate of wildly growing yeasts.

Just as Thompson has redefined the role of AKT, Chi Van Dang, director of the Abramson Cancer Center at the University of Pennsylvania, has helped lead the cancer world to an appreciation of how one widely studied gene can profoundly influence a tumor’s metabolism. In 1997, Dang became one of the first scientists to connect molecular biology to the science of cellular metabolism when he demonstrated that MYC — a so-called regulator gene well known for its role in cell proliferation — directly targets an enzyme that can turn on the Warburg effect. Dang recalls that other researchers were skeptical of his interest in a housekeeping enzyme, but he stuck with it because he came to appreciate something critical: Cancer cells can’t stop eating.

Unlike healthy cells, growing cancer cells are missing the internal feedback loops that are designed to conserve resources when food isn’t available. They’re “addicted to nutrients,” Dang says; when they can’t consume enough, they begin to die. The addiction to nutrients explains why changes to metabolic pathways are so common and tend to arise first as a cell progresses toward cancer: It’s not that other types of alterations can’t arise first, but rather that, when they do, the incipient tumors lack the access to the nutrients they need to grow. Dang uses the analogy of a work crew trying to put up a building. “If you don’t have enough cement, and you try to put a lot of bricks together, you’re going to collapse,” he says.

Metabolism-centered therapies have produced some tantalizing successes. Agios Pharmaceuticals, a company co-founded by Thompson, is now testing a drug that treats cases of acute myelogenous leukemia that have been resistant to other therapies by inhibiting the mutated versions of the metabolic enzyme IDH 2. In clinical trials of the Agios drug, nearly 40 percent of patients who carry these mutations are experiencing at least partial remissions.

Researchers working in a lab run by Peter Pedersen, a professor of biochemistry at Johns Hopkins, discovered that a compound known as 3-bromopyruvate can block energy production in cancer cells and, at least in rats and rabbits, wipe out advanced liver cancer. (Trials of the drug have yet to begin.) At Penn, Dang and his colleagues are now trying to block multiple metabolic pathways at the same time. In mice, this two-pronged approach has been able to shrink some tumors without debilitating side effects. Dang says the hope is not necessarily to find a cure but rather to keep cancer at bay in a “smoldering quiet state,” much as patients treat their hypertension.

Warburg, too, appreciated that a tumor’s dependence upon a steady flow of nutrients might eventually prove to be its fatal weakness. Long after his initial discovery of the Warburg effect, he continued to research the enzymes involved in fermentation and to explore the possibility of blocking the process in cancer cells. The challenge Warburg faced then is the same one that metabolism researchers face today: Cancer is an incredibly persistent foe. Blocking one metabolic pathway has been shown to slow down and even stop tumor growth in some cases, but tumors tend to find another way. “You block glucose, they use glutamine,” Dang says, in reference to another primary fuel used by cancers. “You block glucose and glutamine, they might be able to use fatty acids. We don’t know yet.”

Given Warburg’s own story of historical neglect, it’s fitting that what may turn out to be one of the most promising cancer metabolism drugs has been sitting in plain sight for decades. That drug, metformin, is already widely prescribed to decrease the glucose in the blood of diabetics (76.9 million metformin prescriptions were filled in the United States in 2014). In the years ahead, it’s likely to be used to treat — or at least to prevent — some cancers. Because metformin can influence a number of metabolic pathways, the precise mechanism by which it achieves its anticancer effects remains a source of debate. But the results of numerous epidemiological studies have been striking. Diabetics taking metformin seem to be significantly less likely to develop cancer than diabetics who don’t — and significantly less likely to die from the disease when they do.

Near the end of his life, Warburg grew obsessed with his diet. He believed that most cancer was preventable and thought that chemicals added to food and used in agriculture could cause tumors by interfering with respiration. He stopped eating bread unless it was baked in his own home. He would drink milk only if it came from a special herd of cows, and used a centrifuge at his lab to make his cream and butter.

Warburg’s personal diet is unlikely to become a path to prevention. But the Warburg revival has allowed researchers to develop a hypothesis for how the diets that are linked to our obesity and diabetes epidemics — specifically, sugar-heavy diets that can result in permanently elevated levels of the hormone insulin — may also be driving cells to the Warburg effect and cancer.

The insulin hypothesis can be traced to the research of Lewis Cantley, the director of the Meyer Cancer Center at Weill Cornell Medical College. In the 1980s, Cantley discovered how insulin, which is released by the pancreas and tells cells to take up glucose, influences what happens inside a cell. Cantley now refers to insulin and a closely related hormone, IGF-1 (insulinlike growth factor 1), as “the champion” activators of metabolic proteins linked to cancer. He’s beginning to see evidence, he says, that in some cases, “it really is insulin itself that’s getting the tumor started.” One way to think about the Warburg effect, says Cantley, is as the insulin, or IGF-1, signaling pathway “gone awry — it’s cells behaving as though insulin were telling it to take up glucose all the time and to grow.” Cantley, who avoids eating sugar as much as he can, is currently studying the effects of diet on mice that have the mutations that are commonly found in colorectal and other cancers. He says that the effects of a sugary diet on colorectal, breast and other cancer models “looks very impressive” and “rather scary.”

Elevated insulin is also strongly associated with obesity, which is expected soon to overtake smoking as the leading cause of preventable cancer. Cancers linked to obesity and diabetes have more receptors for insulin and IGF-1, and people with defective IGF-1 receptors appear to be nearly immune to cancer. Retrospective studies, which look back at patient histories, suggest that many people who develop colorectal, pancreatic or breast cancer have elevated insulin levels before diagnosis. It’s perhaps not entirely surprising, then, that when researchers want to grow breast-cancer cells in the lab, they add insulin to the tissue culture. When they remove the insulin, the cancer cells die.

“I think there’s no doubt that insulin is pro-cancer,” Watson says, with respect to the link between obesity, diabetes and cancer. “It’s as good a hypothesis as we have now.” Watson takes metformin for cancer prevention; among its many effects, metformin works to lower insulin levels. Not every cancer researcher, however, is convinced of the role of insulin and IGF-1 in cancer. Robert Weinberg, a researcher at M.I.T.’s Whitehead Institute who pioneered the discovery of cancer-causing genes in the ’80s, has remained somewhat cool to certain aspects of the cancer-metabolism revival. Weinberg says that there isn’t yet enough evidence to know whether the levels of insulin and IGF-1 present in obese people are sufficient to trigger the Warburg effect. “It’s a hypothesis,” Weinberg says. “I don’t know if it’s right or wrong.”

During Warburg’s lifetime, insulin’s effects on metabolic pathways were even less well understood. But given his ego, it’s highly unlikely that he would have considered the possibility that anything other than damaged respiration could cause cancer. He died sure that he was right about the disease. Warburg framed a quote from Max Planck and hung it above his desk: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die.”

After ‘The Biggest Loser,’ Their Bodies Fought to Regain Weight

Danny Cahill stood, slightly dazed, in a blizzard of confetti as the audience screamed and his family ran on stage. He had won Season 8 of NBC’s reality television show “The Biggest Loser,” shedding more weight than anyone ever had on the program — an astonishing 239 pounds in seven months.

When he got on the scale for all to see that evening, Dec. 8, 2009, he weighed just 191 pounds, down from 430. Dressed in a T-shirt and knee-length shorts, he was lean, athletic and as handsome as a model.

“I’ve got my life back,” he declared. “I mean, I feel like a million bucks.”

Mr. Cahill left the show’s stage in Hollywood and flew directly to New York to start a triumphal tour of the talk shows, chatting with Jay Leno, Regis Philbin and Joy Behar. As he heard from fans all over the world, his elation knew no bounds.

But in the years since, more than 100 pounds have crept back onto his 5-foot-11 frame despite his best efforts. In fact, most of that season’s 16 contestants have regained much if not all the weight they lost so arduously. Some are even heavier now.

Yet their experiences, while a bitter personal disappointment, have been a gift to science. A study of Season 8’s contestants has yielded surprising new discoveries about the physiology of obesity that help explain why so many people struggle unsuccessfully to keep off the weight they lose.

Kevin Hall, a scientist at a federal research center who admits to a weakness for reality TV, had the idea to follow the “Biggest Loser” contestants for six years after that victorious night. The project was the first to measure what happened to people over as long as six years after they had lost large amounts of weight with intensive dieting and exercise.

The results, the researchers said, were stunning. They showed just how hard the body fights back against weight loss.
“It is frightening and amazing,” said Dr. Hall, an expert on metabolism at the National Institute of Diabetes and Digestive and Kidney Diseases, which is part of the National Institutes of Health.

“I am just blown away.”

It has to do with resting metabolism, which determines how many calories a person burns when at rest. When the show began, the contestants, though hugely overweight, had normal metabolisms for their size, meaning they were burning a normal number of calories for people of their weight. When it ended, their metabolisms had slowed radically and their bodies were not burning enough calories to maintain their thinner sizes.

Researchers knew that just about anyone who deliberately loses weight — even if they start at a normal weight or even underweight — will have a slower metabolism when the diet ends. So they were not surprised to see that “The Biggest Loser” contestants had slow metabolisms when the show ended.

What shocked the researchers was what happened next: As the years went by and the numbers on the scale climbed, the contestants’ metabolisms did not recover. They became even slower, and the pounds kept piling on. It was as if their bodies were intensifying their effort to pull the contestants back to their original weight.

Mr. Cahill was one of the worst off. As he regained more than 100 pounds, his metabolism slowed so much that, just to maintain his current weight of 295 pounds, he now has to eat 800 calories a day less than a typical man his size. Anything more turns to fat.

‘A Basic Biological Reality’

The struggles the contestants went through help explain why it has been so hard to make headway against the nation’s obesity problem, which afflicts more than a third of American adults. Despite spending billions of dollars on weight-loss drugs and dieting programs, even the most motivated are working against their own biology.

Their experience shows that the body will fight back for years. And that, said Dr. Michael Schwartz, an obesity and diabetes researcher who is a professor of medicine at the University of Washington, is “new and important.”

“The key point is that you can be on TV, you can lose enormous amounts of weight, you can go on for six years, but you can’t get away from a basic biological reality,” said Dr. Schwartz, who was not involved in the study. “As long as you are below your initial weight, your body is going to try to get you back.”

The show’s doctor, Robert Huizenga, says he expected the contestants’ metabolic rates to fall just after the show, but was hoping for a smaller drop. He questioned, though, whether the measurements six years later were accurate. But maintaining weight loss is difficult, he said, which is why he tells contestants that they should exercise at least nine hours a week and monitor their diets to keep the weight off.

“Unfortunately, many contestants are unable to find or afford adequate ongoing support with exercise doctors, psychologists, sleep specialists, and trainers — and that’s something we all need to work hard to change,” he said in an email.

The study’s findings, to be published on Monday in the journal Obesity, are part of a scientific push to answer some of the most fundamental questions about obesity. Researchers are figuring out why being fat makes so many people develop diabetes and other medical conditions, and they are searching for new ways to block the poison in fat. They are starting to unravel the reasons bariatric surgery allows most people to lose significant amounts of weight when dieting so often fails. And they are looking afresh at medical care for obese people.

The hope is that this work will eventually lead to new therapies that treat obesity as a chronic disease and can help keep weight under control for life.

Most people who have tried to lose weight know how hard it is to keep the weight off, but many blame themselves when the pounds come back. But what obesity research has consistently shown is that dieters are at the mercy of their own bodies, which muster hormones and an altered metabolic rate to pull them back to their old weights, whether that is hundreds of pounds more or that extra 10 or 15 that many people are trying to keep off.

There is always a weight a person’s body maintains without any effort. And while it is not known why that weight can change over the years — it may be an effect of aging — at any point, there is a weight that is easy to maintain, and that is the weight the body fights to defend. Finding a way to thwart these mechanisms is the goal scientists are striving for. First, though, they are trying to understand them in greater detail.

Dr. David Ludwig, the director of the New Balance Foundation Obesity Prevention Center at Boston Children’s Hospital, who was not involved in the research, said the findings showed the need for new approaches to weight control. He cautioned that the study was limited by its small size and the lack of a control group of obese people who did not lose weight. But, he added, the findings made sense.

“This is a subset of the most successful” dieters, he said. “If they don’t show a return to normal in metabolism, what hope is there for the rest of us?”

Still, he added, “that shouldn’t be interpreted to mean we are doomed to battle our biology or remain fat. It means we need to explore other approaches.”

Slimmer and Hungrier

Some scientists say weight maintenance has to be treated as an issue separate from weight loss. Only when that challenge is solved, they say, can progress truly be made against obesity.
“There is a lot of basic research we still need to do,” said Dr. Margaret Jackson, who is directing a project at Pfizer. Her group is testing a drug that, in animals at least, acts like leptin, a hormone that controls hunger. With weight loss, leptin levels fall and people become hungry. The idea is to trick the brains of people who have lost weight so they do not become ravenous for lack of leptin.

While many of the contestants kept enough weight off to improve their health and became more physically active, the low weights they strived to keep eluded all but one of them: Erinn Egbert, a full-time caregiver for her mother in Versailles, Ky. And she struggles mightily to keep the pounds off because her metabolism burns 552 fewer calories a day than would be expected for someone her size.

“What people don’t understand is that a treat is like a drug,” said Ms. Egbert, who went from 263 pounds to just under 176 on the show, and now weighs between 152 and 157. “Two treats can turn into a binge over a three-day period. That is what I struggle with.”

Six years after Season 8 ended, 14 of the 16 contestants went to the N.I.H. last fall for three days of testing. The researchers were concerned that the contestants might try to frantically lose weight before coming in, so they shipped equipment to them that would measure their physical activity and weight before their visit, and had the information sent remotely to the N.I.H.
The contestants received their metabolic results last week. They were shocked, but on further reflection, decided the numbers explained a lot.

“All my friends were drinking beer and not gaining massive amounts of weight,” Mr. Cahill said. “The moment I started drinking beer, there goes another 20 pounds. I said, ‘This is not right. Something is wrong with my body.’”

Sean Algaier, 36, a pastor from Charlotte, N.C., feels cheated. He went from 444 pounds to 289 as a contestant on the show. Now his weight is up to 450 again, and he is burning 458 fewer calories a day than would be expected for a man his size.
“It’s kind of like hearing you have a life sentence,” he said.

Losing a Key Hormone

Slower metabolisms were not the only reason the contestants regained weight, though. They constantly battled hunger, cravings and binges. The investigators found at least one reason: plummeting levels of leptin. The contestants started out with normal levels of leptin. By the season’s finale, they had almost no leptin at all, which would have made them ravenous all the time. As their weight returned, their leptin levels drifted up again, but only to about half of what they had been when the season began, the researchers found, thus helping to explain their urges to eat.

Leptin is just one of a cluster of hormones that control hunger, and although Dr. Hall and his colleagues did not measure the rest of them, another group of researchers, in a different project, did. In a one-year study funded by Australia’s National Health and Medical Research Council, Dr. Joseph Proietto of the University of Melbourne and his colleagues recruited 50 overweight people who agreed to consume just 550 calories a day for eight or nine weeks. They lost an average of nearly 30 pounds, but over the next year, the pounds started coming back.

Dr. Proietto and his colleagues looked at leptin and four other hormones that satiate people. Levels of most of them fell in their study subjects. They also looked at a hormone that makes people want to eat. Its level rose.

“What was surprising was what a coordinated effect it is,” Dr. Proietto said. “The body puts multiple mechanisms in place to get you back to your weight. The only way to maintain weight loss is to be hungry all the time. We desperately need agents that will suppress hunger and that are safe with long-term use.”

370, 400, 460, 485

Mr. Cahill, 46, said his weight problem began when he was in the third grade. He got fat, then fatter. He would starve himself, and then eat a whole can of cake frosting with a spoon. Afterward, he would cower in the pantry off the kitchen, feeling overwhelmed with shame.

Over the years, his insatiable urge to eat kept overcoming him, and his weight climbed: 370 pounds, 400, 460, 485.

“I used to look at myself and think, ‘I am horrible, I am a monster, subhuman,’” he said. He began sleeping in a recliner because he was too heavy to sleep lying down. Walking hurt; stairs were agony. Buying clothes with a 68 waist was humiliating.

“I remember sitting in a dressing room one day, and nothing would fit. I looked at the traffic outside on the street and thought, ‘I should just run out in front of a car.’”
He eventually seized on “The Biggest Loser” as his best chance to lose enough weight to live a normal life. He tried three times and was finally selected.

Before the show began, the contestants underwent medical tests to be sure they could endure the rigorous schedule that lay ahead. And rigorous it was. Sequestered on the “Biggest Loser” ranch with the other contestants, Mr. Cahill exercised seven hours a day, burning 8,000 to 9,000 calories according to a calorie tracker the show gave him. He took electrolyte tablets to help replace the salts he lost through sweating, consuming many fewer calories than before.

Eventually, he and the others were sent home for four months to try to keep losing weight on their own.
Mr. Cahill set a goal of a 3,500-caloric deficit per day. The idea was to lose a pound a day. He quit his job as a land surveyor to do it.

His routine went like this: Wake up at 5 a.m. and run on a treadmill for 45 minutes. Have breakfast — typically one egg and two egg whites, half a grapefruit and a piece of sprouted grain toast. Run on the treadmill for another 45 minutes. Rest for 40 minutes; bike ride nine miles to a gym. Work out for two and a half hours. Shower, ride home, eat lunch — typically a grilled skinless chicken breast, a cup of broccoli and 10 spears of asparagus. Rest for an hour. Drive to the gym for another round of exercise.

If he had not burned enough calories to hit his goal, he went back to the gym after dinner to work out some more. At times, he found himself running around his neighborhood in the dark until his calorie-burn indicator reset to zero at midnight.
On the day of the weigh-in on the show’s finale, Mr. Cahill and the others dressed carefully to hide the rolls of loose skin that remained, to their surprise and horror, after they had lost weight. They wore compression undergarments to hold it in.

Mr. Cahill knew he could not maintain his finale weight of 191 pounds. He was so mentally and physically exhausted he barely moved for two weeks after his publicity tour ended. But he had started a new career giving motivational speeches as the biggest loser ever, and for the next four years, he managed to keep his weight below 255 pounds by exercising two to three hours a day. But two years ago, he went back to his job as a surveyor, and the pounds started coming back.

Soon the scale hit 265. Mr. Cahill started weighing and measuring his food again and stepped up his exercise. He got back down to 235 to 240 pounds. But his weight edged up again, to 275, then 295.

His slow metabolism is part of the problem, and so are his food cravings. He opens a bag of chips, thinking he will have just a few. “I’d eat five bites. Then I’d black out and eat the whole bag of chips and say, ‘What did I do?’”

Brain Sets the Calories

Dr. Lee Kaplan, an obesity researcher at Harvard, says the brain sets the number of calories we consume, and it can be easy for people to miss that how much they eat matters less than the fact that their bodies want to hold on to more of those calories.

Dr. Michael Rosenbaum, an obesity researcher at Columbia University who has collaborated with Dr. Hall in previous studies, said the body’s systems for regulating how many calories are consumed and how many are burned are tightly coupled when people are not strenuously trying to lose weight or to maintain a significant weight loss. Still, pounds can insidiously creep on.

“We eat about 900,000 to a million calories a year, and burn them all except those annoying 3,000 to 5,000 calories that result in an average annual weight gain of about one to two pounds,” he said. “These very small differences between intake and output average out to only about 10 to 20 calories per day — less than one Starburst candy — but the cumulative consequences over time can be devastating.”

“It is not clear whether this small imbalance and the resultant weight gain that most of us experience as we age are the consequences of changes in lifestyle, the environment or just the biology of aging,” Dr. Rosenbaum added.

The effects of small imbalances between calories eaten and calories burned are more pronounced when people deliberately lose weight, Dr. Hall said. Yes, there are signals to regain weight, but he wondered how many extra calories people were driven to eat. He found a way to figure that out.

He analyzed data from a clinical trial in which people took a diabetes drug, canagliflozin, that makes them spill 360 calories a day into their urine, or took a placebo. The drug has no known effect on the brain, and the person does not realize those calories are being spilled. Those taking the drug gradually lost weight. But for every five pounds they lost, they were, without realizing it, eating an additional 200 calories a day.

Those extra calories, Dr. Hall said, were a bigger driver of weight regained than the slowing of the metabolism. And, he added, if people fought the urge to eat those calories, they would be hungry. “Unless they continue to fight it constantly, they will regain the weight,” he said.

All this does not mean that modest weight loss is hopeless, experts say. Individuals respond differently to diet manipulations — low-carbohydrate or low-calorie diets, for example — and to exercise and weight-loss drugs, among other interventions.

But Dr. Ludwig said that simply cutting calories was not the answer. “There are no doubt exceptional individuals who can ignore primal biological signals and maintain weight loss for the long term by restricting calories,” he said, but he added that “for most people, the combination of incessant hunger and slowing metabolism is a recipe for weight regain — explaining why so few individuals can maintain weight loss for more than a few months.”

Dr. Rosenbaum agreed. “The difficulty in keeping weight off reflects biology, not a pathological lack of willpower affecting two-thirds of the U.S.A.,” he said.

Mr. Cahill knows that now. And with his report from Dr. Hall’s group showing just how much his metabolism had slowed, he stopped blaming himself for his weight gain.

“That shame that was on my shoulders went off,” he said.

Short Answers to Hard Questions About Weight Loss

Almost everyone who has ever dieted knows how hard it is to keep the weight off. And almost everyone, including many scientists, has wondered what works. An article on Monday about what happened to contestants from “The Biggest Loser” television show is a vivid illustration of the problem. Although there is no magic formula for weight maintenance, here are answers to some questions that arise over and over.

Are you more likely to maintain weight loss if you lose weight slowly?

That is the advice dieters often get, but studies have not found that to be the case. For example, a recent Australian study, funded by the Australian National Health and Medical Research Council and the Sir Edward Dunlop Medical Research Foundation, randomly assigned 204 obese people to subsist on just 450 to 800 calories a day for 12 weeks, or to cut a more modest 400 to 500 calories a day from their diets over 36 weeks. The goal for both groups was a 15 percent weight loss. Three years after the study began, almost everyone had regained the weight they lost, despite counseling on diet and exercise. There was also no difference in the levels of two hormones, leptin and ghrelin, that drive hunger. The main difference between the groups was that more people in the rapid weight loss group lost at least 12.5 percent of their weight (80 percent, compared with 50 percent in the slow loss group) and fewer dropped out (3 percent, compared with 18 percent).

To maintain weight loss, should you avoid snacks?

Although it seems to make sense that snacks can pack on the pounds, studies that randomly assigned people to snack or not have failed to confirm this, and even observational studies have not found evidence that snacks undermine weight loss.

If you build muscle with exercise, including weight lifting, will you be able to maintain a higher metabolism?

Muscle burns more calories than fat, so it might stand to reason that the more muscle you have the faster you will burn calories. But it turns out that building muscles has almost no effect on resting metabolism, which determines how many calories a person burns when at rest. The reason is that any muscle you add is small compared with the total amount of skeletal muscle on your body. And most of the time that muscle is at rest. (You can’t go around flexing your biceps nonstop.) Muscles have a very low metabolic rate at rest. One researcher calculated that if a man weighing about 175 pounds lifts weights and puts on about 4½ pounds of muscle — a typical amount for men who lift weights for 12 weeks — he will burn an extra 24 calories a day, the amount in a couple of Life Saver candies.

Can you defeat your body’s slowed metabolism after weight loss by doing vigorous cardiovascular exercises?

You can as long as you do not eat more calories to make up for the ones you burned. It sounds simple enough, but “this is not as easy a proposition as it sounds,” says Dr. Michael Rosenbaum, a doctor and obesity researcher at Columbia University. The brain controls your hunger and your cravings for food, and it is all too easy to accidentally consume more calories than you burned exercising. That is a major reason studies that use exercise alone to help people lose weight have generally failed to find an effect.

Exercise also has an unexpected effect, documented by Dr. Rosenbaum and Dr. Rudolph Leibel at Columbia University. They found that after you lose 10 percent or more of your weight by diet alone, your muscles start using genes that make them more efficient. They burn 20 to 30 percent fewer calories for the same exercise.

Is there a type of diet that helps keep weight off?

Many people swear by diets that are low in carbohydrates or gluten free, or revolve around fasting two days out of seven. Dr. Lee Kaplan, an obesity researcher at Harvard, says there is no diet or weight-loss regimen that is guaranteed to work but that people can often maintain a loss of 5 percent of their weight, which is enough for health benefits to kick in. He tells his patients to try one weight-loss program after another in hopes of finding something that works for them.

So what hope is there for weight maintenance?

Anecdotal reports by people who have succeeded in keeping weight off tend to have a common theme: constant vigilance, keeping close track of weight, controlling what food is eaten and how much (often by weighing and measuring food), exercising often, putting up with hunger and resisting cravings to the best of their ability. Those who maintain a modest weight loss often report less of a struggle than those trying to keep off large amounts of weight.