Prognosis Positive

1 Playing It to the Bone
Back surgeons, unlike some of their orthopedic colleagues, can’t simply slap a cast over an injury and wait for the bones to heal themselves. Which is why, for decades, scientists have sought a way to stage-manage bone growth. Now doctors at the Hospital for Special Surgery in New York believe they have figured out how to tell the body to grow fresh bone, and to do it much faster than it would on its own, even in delicate areas like the human vertebrae.

Each year, more than 200,000 Americans undergo spinal-fusion surgery as a remedy for chronic back pain. Back pain is usually caused by some sort of instability in the spine, such as a slipped or ruptured disc. Spinal discs act as shock absorbers between the vertebrae. If one ruptures or slips out of place, nerves in the spine get pinched.

In spinal-fusion surgery, the surgeon usually removes the disc altogether and fuses together the two vertebrae that sandwich the troubled disc. Fusion typically requires metal plates and pins, and in order to speed up the process, chips of bone from other parts of the body (or sometimes cadavers) are placed where the surgeon wants new bone to appear. The procedure is very involved and requires a long recuperation period, during which the body creates new bone.

“Something in the body is telling those bones to heal themselves,” says Dr. Harvinder Sandhu, who is leading the trials. “And we are at the stage where we’ve identified the proteins that tell the cells, ‘Okay, now it’s time to make bone; this is where you’re going to make it.’ ” Dr. Sandhu and his colleagues can now artificially reproduce them and place them where new bone growth is needed—usually by dipping a bio-compatible sponge into the liquid protein mix and then placing it where bone is needed. “You’re fooling the body into thinking it’s had a fracture,” he explains.

The result is less-invasive surgery (tiny incisions vs. inches of scar tissue), less spinal trauma, and faster bone regrowth. A patient who would otherwise take six months to fully recover can now be back on his feet in a month or two. And a weeklong hospital stay might turn into same-day surgery. In clinical trials, some patients did, in fact, go home within 24 hours. The trials have been extended to sixteen hospitals throughout the country, and Sandhu hopes to submit results to the FDA soon, which could pave the way for better back surgeries by next year.

2 Combine and Conquer
It’s been almost 40 years since the medical community has made serious inroads in the treatment of colon cancer, the second-deadliest cancer in America. But today there are several new drugs that hold great promise, each with strong New York connections. The first, which was approved in 1996, is called CPT-11 and is being incorporated into a groundbreaking treatment regimen for late-stage patients. The other, called C225, was developed by SoHo-based ImClone Systems and, though still in clinical trials, is already showing encouraging results.

Dr. Leonard Saltz of Memorial Sloan-Kettering and his team not only created the new regimen but have taken the lead on the study of the C225 drug as well. (According to Saltz, C225 is currently a “hot molecule” in cancer circles.) In a nutshell, the C225 drug is an antibody that attaches itself to tumor cells, blocking the signals that tell the tumor cell to grow. It also appears to make tumor cells more vulnerable to radiation or chemotherapy, making them easier to destroy. Dr. Saltz is testing the drug’s impact on colon cancer, but ImClone is also looking at potential benefits for head, neck, and lung cancers as well.

While studying the specific effects of C225, Saltz is also exploring its efficacy in combination with a variety of “boutique” chemotherapies (a dissonant designation if there ever was one) and multiple-drug cocktails tailored to the unique genetics of each tumor. Each of these studies builds on Saltz’s recent successful development of a new chemotherapy treatment for late-stage-colorectal-cancer patients, which involved mixing a traditional cancer-fighting drug known as 5FU with CPT-11. The results, which were published in September, showed almost a doubling of the number of patients whose tumors shrank.

Saltz plans to start testing the therapy on earlier-stage patients; if it’s successful, it may not only extend the lives of the critically ill but perhaps increase the percentage of patients who are cured altogether.

C225 should enter phase III clinical trials (the last stage) this summer and be tested at more than 70 hospitals and research centers around the country, with Saltz as the lead investigator. Its effectiveness is being tested in tandem with established cancer-fighting drugs, and on patients who haven’t responded to traditional chemotherapy treatment. ImClone plans to file for approval with the FDA in May, and because the drug has been fast-tracked, the review process could take as little as six months.

“It’s a very exciting time to be a researcher in colon cancer,” says Saltz. “We’ve started to have higher standards for what we can offer our patients right now. And it’s the tip of the iceberg in terms of what we’re going to be offering in the very near future.”

3 The End of Needles As They Know Them
It used to be that when Ted Calamia ate out, there was always a course that preceded the appetizer, one he’d rather have skipped altogether. Calamia, who is 53 and lives in Park Slope, is diabetic, one of about 500,000 in the New York area. Before unfolding his napkin, he would first prick his finger to measure his blood sugar, then pull out an insulin-filled syringe as discreetly as possible and slip the needle through his pants into his thigh. “Believe me,” he says, “it’s not a fun experience.”

So when he saw an ad last year looking for people to try out a new insulin inhaler at St. Luke’s-Roosevelt Hospital, he jumped at the chance. The inhaler is being tested by New York-based Pfizer (in partnership with New Jersey-based Aventis), which along with the rest of the industry has been searching for an alternative to the needle for almost 75 years. According to Pfizer’s Dr. Michael Berelowitz, scientists have unsuccessfully tried everything from nasal sprays to skin patches. Berelowitz says Pfizer hopes to submit results from clinical trials to the FDA later this year, which means the product could gain approval and become available as early as next year.

Gone untreated, diabetes can lead to blindness, kidney disease, loss of limbs, and even cardiovascular disease in some patients. And fully half of Americans who have the disease don’t even know it. Dr. Gerald Bernstein, who is an endocrinologist at Beth Israel Medical Center and a past president of the American Diabetes Association, thinks there will be a huge psychological advantage to this method of delivery, noting that some people refuse to use needles at all: “If taking the insulin is a simple thing to do, people will be more apt to control their blood sugar and therefore eliminate the complications.”

Dr. Robin Goland, co-director of the Naomi Berrie Diabetes Center at Columbia-Presbyterian Medical Center, is overseeing one of the trials. While she cautions that the device may not work for all diabetics, depending on the specific type of insulin needed (only the short-acting kind is available for now), she says the early indications are that the inhaler will be a welcome addition to the current arsenal. “Both in our experience and from what I’ve read, it looks very successful,” says Goland.

After using the inhaler for seven months, Calamia is down to only one shot a day and feels more comfortable in public. “It’s a lot easier for me to socialize,” he says.

4 An Off-the-Wall Solution
One of the reasons coronary heart disease is the leading killer of Americans is that its primary manifestations – heart attacks and strokes – usually arrive without warning. Many people die within minutes or hours of heart attacks if not treated immediately. But what if you could see them coming?

Dr. Valentin Fuster, who runs the cardiac program for Mount Sinai, and Dr. Zahi Fayad have been working on a new procedure called the Black Blood MRI, which they expect will do just that, and which may eventually be as routine as a mammogram for people who are predisposed to heart disease. “This is the first time that you can go noninvasively and look at the coronary artery,” says Fuster. “Four years ago, no one could even dream this would happen.”

With traditional diagnostic tools such as angiograms, where dye is injected into the body and a catheter is inserted through the groin area and moved up near the heart, doctors can use an X-ray to spot clogged arteries. But a more serious potential problem – plaque build-up on the walls of the coronary, carotid, and aorta arteries – has been hidden from doctors’ eyes until now.

Basically, it’s a twist on an existing MRI technology that allows doctors to change the look of the blood on the image from white to black, thus allowing the walls of the artery to stand out as a white circle when viewed as a cross-section, making the wall alone visible for the first time (previously, the blood and arteries all appeared as one solid white image).

So what’s the big deal? Doctors can now identify places on the artery walls where plaque is building up in little patches (the plaque, which is basically a soft fatty deposit, shows up as a lump on the inner wall of the artery), even if the arteries aren’t “clogged” in the traditional sense. Eventually these hard-to-spot plaque deposits soften and become susceptible to rupture. A rupture can trigger a blood clot that can block an artery and the oxygen that flows through it.

“They’re really on the cutting edge,” says Dr. Richard Lee, a Harvard Medical School research scientist who recently published a study about the dangers of fatty plaque deposits on arterial walls. “What they’re doing is absolutely crucial.”

Dr. Fayad, the 33-year-old who has been refining the technology, says that the hospital is now applying the technology to an average of two patients a day, so far with remarkable success. And once patients have been diagnosed, they can begin drug therapy to reduce the deposits and thus lower the chance of heart attack or stroke. Fayad expects that within a year or two, the technology will be widely available.

5 A Doctor Whose Heart Is in the Right Place
Dr. Robert Jarvik captured the world’s attention in 1982 when he implanted the first artificial human heart. But the device, while revolutionary, was nowhere near ready for prime time. The fact that the first patient lived for several months without his natural heart was extraordinary, but soon after the patient died, Jarvik and the rest of the medical community began to move away from mechanical hearts and toward devices that assisted, rather than replaced, the body’s most important organ.

Fast-forward to 2001. After fourteen years on the drawing boards, the Jarvik 2000, which he calls an “intra-ventricular heart,” is now in clinical trials. It’s essentially a small titanium pump (about the size of a C battery) that keeps your blood flowing through the weakened left ventricle should you experience heart failure. It’s part of a new generation of pulmonary hardware that provides a “continuous flow” of blood – like a mini-propeller in a tube – as opposed to more traditional pumping devices, which are much bigger and create an externally audible pumping sound. Jarvik thinks artificial pumps like these could save as many as 100,000 people per year in the U.S. alone whose own hearts would otherwise give out.

At the Texas Heart Institute, where trials are being conducted, the Jarvik 2000 has already been implanted in nine patients awaiting heart transplants. But since there are only about 2,000 human hearts available for transplant each year, Jarvik is most excited about a clinical trial under way in England in which three people have received the pump as
a “permanent” solution, meaning they were not awaiting a transplant; instead, the pump will remain inside them for the duration of their lives. (So far, two have survived.) Jarvik hopes to apply for FDA approval to conduct similar permanent-usage trials in the U.S. early next year. “Our goal is to make the Jarvik 2000 as common as a pacemaker,” he says.

Dr. Mehmet Oz, director of the mechanical-heart program at Columbia-Presbyterian, says that the newest round of continuous-flow heart pumps, including the Jarvik 2000, represents a huge leap in terms of treating patients. He believes that these pumps will eventually enable doctors to extend the lives of patients now considered too old or sick to receive replacement hearts.

In fact, Dr. Oz, who did a heart transplant for Frank Torre (Joe’s brother), has been leading nationwide clinical trials to determine whether elderly patients can benefit from the technology. So far, the Columbia results are promising, with some patients living as long as two years using a pump. He hopes to begin implanting the new pumps within three months. “It’s a big change for us,” says Oz. “It’s like the original Macintosh coming with a whole new operating system.”

6 An Eczema Solution That’s More Than Skin-Deep
Three years ago, when Stephanie Armenti was 4, she asked her mom why her chicken pox wasn’t going away. But Stephanie, who had endured red, itchy, irritated skin since she was only a year old, didn’t have chicken pox. She actually had, and still has, eczema, a skin condition that plagues more than 15 million people in the U.S, mostly children.

Stephanie’s mother, Jacqueline, learned that NYU was looking for eczema sufferers to participate in clinical trials and began bringing her daughter from their home in Middletown, New Jersey, to the NYU Medical Center each week to help test a new ointment that appears to be the first significant step in treating eczema in decades. “It’s a major advance,” says Dr. Irwin Freedberg, chairman of the dermatology department at NYU School of Medicine. “It’s a totally different approach, interfering with parts of the immune system that are really the effectors of what you see on the skin.”

Eczema is an immunological reaction to physical or psychological irritants. (Because heat, stress, and airborne irritants are among the worst offenders, Dr. Freedberg says that dense urban environments like New York City can be especially hard on eczema sufferers.) Since 1960, the only significant treatment for eczema has been topical cortisone, a steroid-based cream. Cortisone sometimes causes side effects like burning, thinning of the skin, and the visible appearance of blood vessels near the surface of the skin, and kids are often steered away from using it because of its steroid content. “Every time I went to a dermatologist,” says Jacqueline, “they gave me cortisone, cortisone, cortisone. She’s little. I don’t know the long-term effects.”

For the past two years, NYU has been one of the lead test centers in the U.S. for clinical trials of several ointments. The one used by Stephanie is made by Fugisawa Healthcare of Japan. It’s the first steroid-free topical ointment that suppresses the reaction of the immune system on the skin’s surface. It was approved by the FDA in December, and became available under the name Protopic just last month.

And not a moment too soon. “When we first went into NYU,” explains Jacqueline, “she was covered everywhere except her trunk.” And during the summer, her skin was splotchy-looking, because areas affected by eczema don’t tan. But after a year of applying the ointment once a day as needed, her skin looks better than it ever has. And while some people experience slight burning as a side effect, Stephanie has not. “She can sleep a whole night now without itching,” says her mom. “And she’s not as cranky.”

7 It’s a Cinch to Lose Weight
With America getting fatter by the minute, it’s no surprise that obesity-related surgeries are now among the fastest-growing in the country; more than 40,000 were performed last year. Most decrease the amount of food that can be digested or absorbed by removing part of the stomach or small intestine. Carnie Wilson became the poster child for this type of surgery after she lost 150 pounds. A new variation, now being tested in New York, promises a safer, less dramatic alternative.

Mount Sinai is leading a nationwide clinical trial to evaluate the effectiveness and safety of a new device called a laparoscopic band, or lap band in industry parlance. The idea: Instead of surgically dividing the stomach, doctors insert a small silicone band, like a tiny belt, by means of laparoscopic surgery (through small incisions in the abdomen, about an inch across), and cinch it around a portion of the stomach to limit the amount of food that can pass through. While not quite as dramatically effective as other methods, the lap band is believed to be safer, with less recovery time and easier reversibility than other versions of this surgery.

Dr. Michel Gagner, chief of laparoscopic surgery for the Mount Sinai School of Medicine, says lap-band surgery is already approved and wildly popular in Europe, and that patients typically lose between 25 and 30 percent of their total weight within a year. Once formal approval has been given in the United States (which could happen within months), Gagner expects the lap band to quickly become a popular choice for patients who are uncomfortable with the complexity and severity of a traditional gastric bypass.

8 The Next Generation of HIV Drugs
Since 1996, the protease-inhibitor cocktail has extended the life spans of millions of people infected with HIV. But that was simply one step, admittedly a huge one, in the battle against AIDS. Soon, David Ho and his team at the Aaron Diamond AIDS Research Center at Rockefeller University, who were at the forefront with protease-inhibitors, hope to begin human clinical trials of a drug, made by New Jersey-based Schering-Plough, that is the first of a new class of drugs designed to fight HIV.

These new drugs are known as entry inhibitors, and they do pretty much what the name suggests. Unlike protease inhibitors, which stem the growth of the virus after it is already inside the cell, entry inhibitors are designed to prevent the virus from getting in the door in the first place.

Here’s how they work: Certain cells in the body have two docking points where a virus can attach itself and then enter. One of these docking points, or co-receptors, is called CCR5. The idea behind the new drugs is that if you can block the CCR5 docking point, the virus can’t get in. Entry inhibitors won’t replace protease inhibitors as a treatment option; rather, they’ll open a new line of attack. Ho is cautiously optimistic. “Our excitement is reminiscent of the excitement we had when, in 1994, we first put these protease inhibitors into patients,” he says. “And they obviously have had a tremendous impact.”

In addition to studying the entry inhibitors, Ho and his team are also starting production of two vaccines they have been developing over the past three years. He says that because the need is currently greater in places like Africa (where 26 million people are estimated to be carrying HIV) and the Far East, they will first seek approval from foreign regulatory bodies, which often move faster than the FDA.

The FDA, however, has quickened the pace when it comes to HIV. “In the AIDS field, the drug-development process has been shortened considerably,” says Ho. “If you look at protease inhibitors, we first put them into patients in 1994, and they were licensed in early 1996. That’s remarkable compared to the usual time line for drug development.”

9 A Picture Worth a Thousand Tubes
Imagine a tiny submarine floating through your body, taking pictures and examining your innards for signs of disease. It may sound like a scene from the sci-fi flick Innerspace, but it’s actually a reality (minus the miniature Dennis Quaid), and for the moment it’s available only in New York.

For people who may have tumors or bleeding in their small intestines, there now exists a tiny camera, complete with a flash and a battery, that can be swallowed like a pill and that snaps more than 50,000 pictures as it winds its way through you. It can uncover a host of problems that standard methods (which are not only incomplete but unpleasant) often miss. In fact, it’s already been tested on more than twenty New Yorkers, and if the FDA approves it, you, or someone you know, may very well be swallowing it within a year.

The pill, which is the size of a large vitamin, is equipped with four flashing LEDs, which illuminate in time with the pictures. As each picture is taken (at a rate of about two per second), the images are wirelessly transmitted to a mini hard drive on your belt. The camera passes through you in roughly twelve hours, at which point it is, well, flushed into retirement.

An Israeli company called Given Imaging has been working on the pill for years, and last October, Dr. Blair Lewis of the Mount Sinai School of Medicine launched clinical trials on humans. Those trials are now complete. According to Lewis, the results, which will have been submitted to the FDA for review, were better than expected.

“It is a phenomenal tool,” says Lewis, who has been comparing the results of the pill with those of a standard enteroscopy, where a tube with a camera in it is used to examine the twenty feet of a person’s small intestine for things like internal bleeding, tumors, and ulcers. “We were very effective in diagnosing causes of bleeding, and there was no diagnosis the enteroscope made that the capsule didn’t make. In some ways, some of the data is better than what’s available now.” That’s because the pill runs the length of the entire small intestine, reaching places that an enteroscope can’t. In two cases during the trials, tumors were spotted that the standard enteroscopy missed. If the camera pill gains approval later this year, regular enteroscopy may have a run for its money.

Dr. Jeffrey Peters, a professor of surgery at USC and a former president of the Society of American Gastrointestinal Endoscopic Surgeons, thinks the pill, for all it’s Buck Rogers pizzazz, has a very real future in the world of endoscopy. “The idea that you could swallow a camera and have it examine your insides has always been out there as a futuristic concept,” he says. “But here it is. It’s real and it works.”

10 Image Is Everything
While prostate cancer is one of the most common cancers, it’s also one of the most curable if caught early. Once it’s been detected, the key is getting a good read on exactly how far along the cancer is and picking the right treatment. The treatment a patient receives – from drugs to radiation and surgery – has always been based largely on educated guesswork. That’s changing.

For several years, Memorial Sloan-Kettering has been one of only two hospitals in the country working with magnetic resonance spectroscopy, a new technology that not only displays physical images of the prostate (with a garden-variety MRI) but also provides more detailed information about the exact location of the tumor as well as key data about its chemical makeup that tell the doctor how aggressive the tumor has become.

So how does this help? Well, for one, a radiologist can now target the tumor with far more accuracy and can apply appropriate doses based on the tumor’s position and chemical makeup. And if surgery is necessary, it gives surgeons a road map to the tumor’s precise location, making the surgery less exploratory.

The technology has been tested on nearly 400 patients at Sloan-Kettering alone. So far, the biggest beneficiaries are patients with early-stage cancer that is highly curable. That’s because they have pretty clear choices of treatment. “If it’s very curable,” explains Dr. Jason Koutcher, “you go for the money – either the surgery or the radiation.”

Dr. Hedvig Hricak, the chair of radiology for Sloan-Kettering, expects that FDA approval for the new software and procedure will likely come later this year, with a wide distribution of the technology, which is being developed and manufactured by General Electric, within a year or so. “We are moving away from looking at anatomy only, and now we are looking at the anatomy and function,” she says. “And that has been the biggest step forward in our ability to assess the disease.”

Prognosis Positive