n the United States, physicians recommend that adults get screening colonoscopies, in which an endoscope is used to look at the lower part of the gastrointestinal tract, where colon cancer can occur. But this lower endoscopy doesn’t cover the stomach and other “upper” areas of the digestive system.

In Asia, however, gastroenterologists use an endoscope to examine the upper part of the gastrointestinal tract for signs of early cancer in adults every few years. That means most cases of gastric cancer there are identified much earlier, and the survival rate in Asia is better than in the United States.

Hwang and his colleagues have been studying the incidence of gastric cancer in the United States and the most at-risk populations, and think that regular screening within certain populations could help reduce mortality here.

GASTROENTEROLOGIST JOO HA HWANG IS ONE OF JUST A FEW DOCTORS IN THE COUNTRY PERFORMING INNOVATIVE ENDOSCOPIC PROCEDURES TO TREAT CANCERS AND OTHER DISEASES OF THE ESOPHAGUS AND STOMACH.

Over the past decade, gastroenterologists in eastern Asia have perfected techniques that allow them to perform new procedures on the esophagus, stomach, and colon using an endoscope—a thin flexible tool that can snake through the digestive tract. The noninvasive techniques not only treat certain gastrointestinal diseases, but are helping lower the mortality rate from gastric cancer by offering a new, non-surgical way of removing precancerous and early cancerous lesions before they grow.

These experimental methods, however, have been slow to catch on in the United States. At Stanford, gastroenterologist Joo Ha Hwang, MD, PhD, professor of medicine, wants to change that. Hwang is leading the way in performing and studying these new esophageal approaches and advocating for better gastric cancer screening. “These procedures, which we’re helping to further develop and study, really represent the cutting-edge medicine that we’re delivering here at Stanford,” says Hwang.

An At-Risk Population
Gastric cancer is the fifth most common cancer worldwide, but its incidence in the United States is relatively low—about 27,000 people are diagnosed with stomach cancer each year. Its prevalence is highest in people of Asian, Pacific Islander, and Hispanic descent, but even among these populations, there are no official screening guidelines in this country.

“It tends to be diagnosed at a late stage here, because the early stage cancer often doesn’t have symptoms,” says Hwang. “That means the survival rate is not very good.”

In the United States, physicians recommend that adults get screening colonoscopies, in which an endoscope is used to look at the lower part of the gastrointestinal tract, where colon cancer can occur. But this lower endoscopy doesn’t cover the stomach and other “upper” areas of the digestive system.

In Asia, however, gastroenterologists use an endoscope to examine the upper part of the gastrointestinal tract for signs of early cancer in adults every few years. That means most cases of gastric cancer there are identified much earlier, and the survival rate in Asia is better than in the United States.

Hwang and his colleagues have been studying the incidence of gastric cancer in the United States and the most at-risk populations, and think that regular screening within certain populations could help reduce mortality here. In 2020, they’ll be hosting a gastric cancer summit at Stanford. “We’re bringing in leaders in gastric cancer from all over the world to talk about how we can establish screening guidelines for high-risk populations in the U.S.,” says Hwang.

Less Invasive Surgery
The push toward increased gastric cancer screening is, in part, due to a relatively new procedure to help remove pre-cancerous and early cancerous lesions from the stomach. Until recently, such lesions could be seen and biopsied using the endoscope, but removing them required surgery.

Now, specially trained gastroenterologists—like Hwang, who went to Korea and Japan for training—can surgically remove the pre-cancers and early cancers endoscopically. The procedure, called an endoscopic submucosal dissection (ESD), takes only a few hours. Patients can generally go home the following day, rather than staying in the hospital several nights as they might after a typical surgery.

“Stanford is now one of the highest volume sites in the United States for ESD,” says Hwang. “We get patients not only from Northern California, but from Hawaii, Alaska, and really all over the country.”

There’s another procedure in the upper digestive tract that’s also heralding a shift from more invasive surgeries toward endoscopic versions. It’s called per-oral endoscopic myotomy, or POEM, and it involves cutting into the muscles that surround the esophagus. Like with ESD, Hwang learned the approach abroad and is now one of the leading POEM providers in the United States. He uses it to treat two conditions—achalasia and gastroparesis.

In achalasia, patients have trouble swallowing because the ring-shaped muscle between the esophagus and stomach doesn’t relax normally, trapping food in the esophagus. Before POEM, the mainstay treatments for achalasia were Botox injections—which relax the muscles, but only for a few months—or surgery.

In POEM, Hwang can use a small knife passed through an endoscope to cut through the inner layers of the esophagus to access the muscle and make a slit in it. Then the esophagus is closed with tiny clips.

“Patients can’t feel the incision or clips, and they can swallow right away. It’s one of the most gratifying procedures I do,” says Hwang.

In another version of POEM, known as gastric per-oral endoscopic myotomy, or G-POEM, the same approach is used to cut the muscle at the base of the stomach, the pylorus, for people with gastroparesis. In this more common disease, the stomach can’t empty itself of food in a normal fashion, leading to heartburn, nausea, vomiting, and feeling full quickly when eating.

Collaborative Research
As the number of esophageal endoscopy procedures offered at Stanford grows, the Esophagus Center is becoming a dynamic epicenter for collaboration and research. Hwang works with other gastroenterologists as well as surgeons and otolaryngologists.

“We are very integrated with the surgery department, and it’s a very multidisciplinary collaborative group,” says Hwang. He’s also working closely with the Stanford Medicine Center for Asian Health Research and Education (CARE) on his gastric cancer screening efforts.

Research questions remain, such as which patient populations benefit most from ESD and POEM, and what are the underlying causes of achalasia and gastroparesis. During POEM procedures, Hwang takes biopsies that may help answer these questions.

The numbers of ESD and POEM cases at Stanford are some of the highest in the country. There are very few training opportunities in the United States for physicians to learn these cutting-edge procedures. Hwang hopes that changes in the near future: “We hope to offer a fellowship training program in these eventually, to help disseminate the knowledge and techniques so that other patients may benefit from these procedures.”

A novel treatment using CAR-T cells is showing promise for treating multiple myeloma. Understanding the treatmet requires a short course in cell therapy (see sidebar). 

Liedtke explains that the treatment uses the patient’s own T cells, which reside in the body after eradicating the cancer.

Her expertise in CAR-T cells derives from her connection with Crystal Mackall, MD, Ernest and Amelia Gallo Family Professor of Pediatrics and Internal Medicine, and founder of the Stanford Center for Cancer Cell Therapy.

For most of us, a common cold or a stomach bug is a nuisance, but usually in a matter of days the body’s immune system will fight off the invading disease-causing agents and we’ll get back to normal. In more serious situations, the immune system even defeats pneumonia, endocarditis, and other severe health threats.

But that’s not the case for the 20,000 to 30,000 Americans who are diagnosed with multiple myeloma each year. Multiple myeloma is a form of cancer that affects plasma cells, the white blood cells in the bone marrow that produce antibodies to fight disease and infection.

Current treatment options include chemotherapy, radiation therapy, specialized drugs, and stem cell transplants. Despite advances in these approaches, the average American will succumb to multiple myeloma about seven to 10 years after being diagnosed with the disease.

“While we can treat the disease well initially, almost every single patient with multiple myeloma relapses, and every time the disease comes back, it becomes more resistant to therapies, making it even harder to treat,” says Michaela Liedtke, MD, associate professor of hematology.

A novel treatment using CAR-T cells is showing promise for treating multiple myeloma. Understanding the treatmet requires a short course in cell therapy (see sidebar).

Liedtke explains that the treatment uses the patient’s own T cells, which reside in the body after eradicating the cancer.

Her expertise in CAR-T cells derives from her connection with Crystal Mackall, MD, Ernest and Amelia Gallo Family Professor of Pediatrics and Internal Medicine, and founder of the Stanford Center for Cancer Cell Therapy.

Liedtke’s research on the subject was part of a study published in the May 2, 2019 issue of The New England Journal of Medicine.

“With this new CAR-T cell technology, known as BB 2121, ultimately the hope is that it will cure the disease and make it go away forever,” Liedtke proclaims.

“If any other cancer cells should develop in the future—if a relapse should ever occur—then the CAR-T cells should be ready to address that relapse or alternatively additional CAR-T cells could be infused. That’s the theoretical context,” she says.

In fact, CAR-T cell technology has proven to be effective in treating acute lymphoblastic leukemia (ALL), especially in children.

“There are studies using similar CAR-T cells showing that half to two-thirds of children with relapsed ALL, another hematological cancer, can be cured of their disease,” she says.

What Are CAR-T Cells?
T cells, part of the immune system that defends the body against infections, can become compromised when a patient develops a malignancy. One way to overcome that is to remove the T cells from the patient’s body and “re-educate” them in the laboratory. That is, each T cell is given a chimeric antigen receptor (CAR), which is why these engineered biological units are known as CAR-T cells.

After the T cells have been converted to CAR-T cells, they are reintroduced into the patient’s bloodstream and circulate in the body. The CAR-T cells are able to recognize, hunt for, and bind to certain characteristics on the surface of cancer cells before destroying them.

The CAR-T cells become very prolific and recreate themselves in great numbers. These expanded numbers of CAR-T cells circulate throughout the body and continue to hunt for myeloma cells until all the malignant cells are destroyed.

Liedtke’s research on the subject was part of a study published in the May 2, 2019 issue of The New England Journal of Medicine.

“With this new CAR-T cell technology, known as BB 2121, ultimately the hope is that it will cure the disease and make it go away forever,” Liedtke proclaims.

“If any other cancer cells should develop in the future—if a relapse should ever occur—then the CAR-T cells should be ready to address that relapse or alternatively additional CAR-T cells could be infused. That’s the theoretical context,” she says.

In fact, CAR-T cell technology has proven to be effective in treating acute lymphoblastic leukemia (ALL), especially in children.

“There are studies using similar CAR-T cells showing that half to two-thirds of children with relapsed ALL, another hematological cancer, can be cured of their disease,” she says.

What Are CAR-T Cells?
T cells, part of the immune system that defends the body against infections, can become compromised when a patient develops a malignancy. One way to overcome that is to remove the T cells from the patient’s body and “re-educate” them in the laboratory. That is, each T cell is given a chimeric antigen receptor (CAR), which is why these engineered biological units are known as CAR-T cells.

After the T cells have been converted to CAR-T cells, they are reintroduced into the patient’s bloodstream and circulate in the body. The CAR-T cells are able to recognize, hunt for, and bind to certain characteristics on the surface of cancer cells before destroying them.

The CAR-T cells become very prolific and recreate themselves in great numbers. These expanded numbers of CAR-T cells circulate throughout the body and continue to hunt for myeloma cells until all the malignant cells are destroyed.

Weissman and his colleagues later developed the Hu5F9-G4 antibody that blocks the CD47 protein, prompting macrophages to engulf and devour cancer cells.

For this clinical trial, participants were administered a combination of Hu5F-G4 and the rituximab antibody that has been shown to amplify positive “eat me” signals.

The antibody combination was used to treat people with two types of non-Hodgkin’s lymphoma: diffuse large B-cell lymphoma and follicular lymphoma.

“It’s very exciting to have a potentially new class of immunotherapy like this,” says Advani. “For the first time we have an antibody that activates macrophages against cancer and appears to be safe for use in humans.”

A novel immunotherapy combination appears safe for use in patients with a type of blood cancer called non-Hodgkin’s lymphoma. Not only that, but half of the 22 people enrolled in an early clinical trial of the therapy had a positive response, and about one-third went into complete remission from their cancer.

The therapy combines Hu5F9-G4 (an experimental antibody developed by researchers at Stanford) and a commercially available anti-cancer antibody called rituximab.

“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” says Ranjana Advani, MD, professor of medicine at Stanford. Advani is the lead author of a paper describing the results of the phase-1 trial that was published in The New England Journal of Medicine.

Some patients showed signs of a transitory anemia or reactions at the injection site, but there were few other significant side effects to the treatment, according to the paper.

Although there are many things that can kill cancer cells, the real test of a therapy is whether it can kill the cancer cells without harming normal cells. Advani says she was particularly pleased that the researchers observed only minor side effects in the participants.

How the Combination Works
In 2010, researchers led by Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, showed that the CD47 protein that covers nearly all cancer cells acts as a “don’t eat me” signal to immune cells called macrophages.

Weissman and his colleagues later developed the Hu5F9-G4 antibody that blocks the CD47 protein, prompting macrophages to engulf and devour cancer cells.

For this clinical trial, participants were administered a combination of Hu5F-G4 and the rituximab antibody that has been shown to amplify positive “eat me” signals.

The antibody combination was used to treat people with two types of non-Hodgkin’s lymphoma: diffuse large B-cell lymphoma and follicular lymphoma.

“It’s very exciting to have a potentially new class of immunotherapy like this,” says Advani. “For the first time we have an antibody that activates macrophages against cancer and appears to be safe for use in humans.”

A Personal Trial
Clinical trial participant Michael Stornetta, a retired Santa Rosa businessman who said he had never previously been sick with anything worse than colds, flus, and the usual childhood maladies, was hit with follicular lymphoma over five years ago. He said that after attempting multiple therapies with “varying degrees of success,” he was referred to the Hu5F9-G4 trial at Stanford.

In October of 2017, he drove with his wife and son to Stanford to view the first scans that would reveal whether the experimental treatment was working. The scans showed that his cancer was significantly reduced. By strange coincidence, the very day he learned that he had lost his house in a devastating wildfire, he also learned that the treatment was working.

A Personal Trial
Clinical trial participant Michael Stornetta, a retired Santa Rosa businessman who said he had never previously been sick with anything worse than colds, flus, and the usual childhood maladies, was hit with follicular lymphoma over five years ago. He said that after attempting multiple therapies with “varying degrees of success,” he was referred to the Hu5F9-G4 trial at Stanford.

In October of 2017, he drove with his wife and son to Stanford to view the first scans that would reveal whether the experimental treatment was working. The scans showed that his cancer was significantly reduced. By strange coincidence, the very day he learned that he had lost his house in a devastating wildfire, he also learned that the treatment was working.

A Growing Population
As of 2019, the population of cancer survivors in the United States has grown to 17 million people. Improved treatments and earlier detection methods mean that people live longer after a cancer diagnosis than ever before—many decades, in some cases. That growing population has led to the emergence of cancer survivorship as a niche field within medicine.

In recent years, it has become popular for oncology clinics around the country to offer patients a survivorship care plan—a one- or two-page document that outlines the patient’s history with cancer, any potential long-term problems they might experience, and recommendations for follow-up care or screening tests.

PRIMARY CARE PHYSICIAN JENNIFER KIM IS HELPING PATIENTS BRIDGE THE GAP BETWEEN CANCER TREATMENT AND THE REST OF THEIR LIVES.

Every cancer patient hopes for a clean scan or blood test showing that all signs of cancer have disappeared. But it doesn’t always mean the end of the cancer story. Compared with the rest of the population, cancer survivors are at an increased risk of recurrence and second tumors. They also can have a host of complex physical, emotional, and psychosocial concerns related to their disease.

Many survivors are plagued by a fear of their cancer returning, and the anxiety can manifest itself in many ways. Treatments can also leave patients with ongoing nerve pain, lung and heart problems, or fertility issues.

Finding a health care provider to address those issues can be tricky. While oncologists can’t keep seeing patients indefinitely after signs of their cancer have disappeared, primary care physicians can be wary of answering patients’ questions that might relate to an oncology diagnosis. It leaves patients in an awkward position.

“People often feel a little bit lost when their oncologist, who they’ve been seeing regularly for months or years, says they’re doing great and don’t need to come back,” says Jennifer Kim, MD, a clinical assistant professor of medicine who is piloting a cancer survivorship clinic at Stanford.

Through her new clinic, Kim is helping bridge the gap between oncology and primary care, ushering both patients and health care providers through this transition.

A Growing Population
As of 2019, the population of cancer survivors in the United States has grown to 17 million people. Improved treatments and earlier detection methods mean that people live longer after a cancer diagnosis than ever before—many decades, in some cases. That growing population has led to the emergence of cancer survivorship as a niche field within medicine.

In recent years, it has become popular for oncology clinics around the country to offer patients a survivorship care plan—a one- or two-page document that outlines the patient’s history with cancer, any potential long-term problems they might experience, and recommendations for follow-up care or screening tests.

“Even when this is done, the information in the document isn’t always being fully communicated to primary care doctors,” says Kim.

Oncology programs have also started looking for other ways to ease patients through the transition from cancer treatment to more routine medical care, including integrating primary care doctors into their practices more closely.

Launching a Clinic
Two years ago, breast oncologist Lidia Schapira, MD, approached Kim about starting a survivorship clinic. First, Kim had to read up on what Schapira meant.

“In all my training, I hadn’t even heard of the word survivorship,” says Kim.

But the more she read—and the more meetings and seminars on survivorship she attended—the more intrigued she became. She agreed to start a pilot program; she spent time shadowing oncologists at Stanford so she’d better understand the ins and outs of cancer treatment. Then she set aside two half-days a week to see patients with breast and gynecologic cancers from the Stanford Women’s Cancer Center.

She helped address specific problems each patient might be having, whether or not the issues were related to a tumor, and set up a long-term plan for cancer screening and primary care needs. The model was immediately successful, with positive feedback from patients and oncologists alike, and Kim’s schedule filled. Since then, she’s expanded to see people who are survivors of lung, colon, and childhood cancers.

For some people, one appointment with Kim is enough to send them on their way with a plan. For others, it may require months of follow-up before they feel ready to move to another primary care provider. In either case, Kim gives them information to pass along to their doctor—or, if they’re continuing to receive care at Stanford, she might call or message the primary care provider directly.

“The advantage of me doing this instead of an oncologist is that I know what most primary care doctors can understand,” says Kim. “I try to hand off recommendations that are manageable and not full of the kind of detail and inside jargon that oncologists might use.”

Survivorship Education for Doctors
Kim can see only so many patients, but her hope is that as more primary care doctors become aware of the unique needs of cancer survivors, others will step up. To that end, Kim and Schapira designed an online continuing education course for primary care doctors to learn key points about survivorship—common long-term and delayed effects of chemotherapy and radiation, for instance.

“You don’t need to be a survivorship expert to integrate these things into your everyday practice,” says Kim. For instance, if someone who once had prostate cancer treatment complains of frequent urination to their primary care doctor, they might normally test for diabetes or pelvic floor issues. But simply being aware that this can be a delayed complication of prostate cancer treatment can help them treat it more appropriately.

She thinks that with a little extra education, primary care doctors can become more comfortable treating cancer survivors. Rather than referring these patients back to oncologists, primary care physicians armed with the right knowledge can handle many of the long-term effects of cancer and cancer treatment on their own.

“Survivorship is a chronic disease, just like diabetes and high blood pressure,” says Kim. “So it’s appropriate for primary care doctors to manage these patients who need a little extra care; it’s just that some training is needed for us to get there.”

“Even when this is done, the information in the document isn’t always being fully communicated to primary care doctors,” says Kim.

Oncology programs have also started looking for other ways to ease patients through the transition from cancer treatment to more routine medical care, including integrating primary care doctors into their practices more closely.

Launching a Clinic
Two years ago, breast oncologist Lidia Schapira, MD, approached Kim about starting a survivorship clinic. First, Kim had to read up on what Schapira meant.

“In all my training, I hadn’t even heard of the word survivorship,” says Kim.

But the more she read—and the more meetings and seminars on survivorship she attended—the more intrigued she became. She agreed to start a pilot program; she spent time shadowing oncologists at Stanford so she’d better understand the ins and outs of cancer treatment. Then she set aside two half-days a week to see patients with breast and gynecologic cancers from the Stanford Women’s Cancer Center.

She helped address specific problems each patient might be having, whether or not the issues were related to a tumor, and set up a long-term plan for cancer screening and primary care needs. The model was immediately successful, with positive feedback from patients and oncologists alike, and Kim’s schedule filled. Since then, she’s expanded to see people who are survivors of lung, colon, and childhood cancers.

For some people, one appointment with Kim is enough to send them on their way with a plan. For others, it may require months of follow-up before they feel ready to move to another primary care provider. In either case, Kim gives them information to pass along to their doctor—or, if they’re continuing to receive care at Stanford, she might call or message the primary care provider directly.

“The advantage of me doing this instead of an oncologist is that I know what most primary care doctors can understand,” says Kim. “I try to hand off recommendations that are manageable and not full of the kind of detail and inside jargon that oncologists might use.”

Survivorship Education for Doctors
Kim can see only so many patients, but her hope is that as more primary care doctors become aware of the unique needs of cancer survivors, others will step up. To that end, Kim and Schapira designed an online continuing education course for primary care doctors to learn key points about survivorship—common long-term and delayed effects of chemotherapy and radiation, for instance.

“You don’t need to be a survivorship expert to integrate these things into your everyday practice,” says Kim. For instance, if someone who once had prostate cancer treatment complains of frequent urination to their primary care doctor, they might normally test for diabetes or pelvic floor issues. But simply being aware that this can be a delayed complication of prostate cancer treatment can help them treat it more appropriately.

She thinks that with a little extra education, primary care doctors can become more comfortable treating cancer survivors. Rather than referring these patients back to oncologists, primary care physicians armed with the right knowledge can handle many of the long-term effects of cancer and cancer treatment on their own.

“Survivorship is a chronic disease, just like diabetes and high blood pressure,” says Kim. “So it’s appropriate for primary care doctors to manage these patients who need a little extra care; it’s just that some training is needed for us to get there.”

Another factor in Watford’s decision had to do with an American Society of Nephrology (ASN) meeting in 2016 “where I was a ‘Kidney STARS’ participant. This program aims to stimulate interest in nephrology among medical students and residents through travel funding to attend the ASN national meeting as well as a multitude of networking opportunities. While attending the meeting in Chicago I met the chief of nephrology, Glenn Chertow, and several other Stanford faculty members during a social event. The combination of that opportunity and my connection with Dimitri spearheaded me coming here.”

Watford met his wife, who was originally from Seattle, at a pre-med summer program at Yale in 2007. She did both undergraduate and medical school at the University of Washington before residency in Miami. 

Two current nephrology fellows share a common background through their residencies at University of Miami/Jackson Memorial Hospital in Florida. Since coming to Stanford two years apart for fellowship, their pathways have diverged somewhat, although their long-term dedication to nephrology and their friendship is unchanged.

Dimitri Augustin, MD, MS, is a fourth-year postdoctoral fellow in nephrology who grew up in South Florida and received both his undergraduate and medical degrees from the University of Miami. He earned a master’s in biochemistry and molecular biology with a biotechnology focus at Georgetown University before medical school. Those studies “opened my eyes to ask how translational research, biotechnology, and medical devices can fit together,” he says. During the third year of his internal medicine residency in Miami, he met Daniel Watford, MD, MPH, a first-year resident.

Watford, currently a second-year fellow in the division of nephrology, was born and raised in Durham, North Carolina. He did his undergraduate work at Princeton University followed by medical school and a master’s of public health at UNC–Chapel Hill. The next step in his career provided the first opportunity for him and his wife to live in the same city. “I couples-matched with my wife, who is an anesthesiologist—now in chronic pain medicine—to Jackson Memorial Hospital in Miami for residency,” he says. “I completed three years of residency and a year of chief residency there.”

Watford’s Trek
Watford explains his cross-country path to Stanford: “I got acquainted with Stanford in a couple of ways. One was through Dimitri Augustin who was one of my senior residents when I was an intern. We hit it off early, initially in more of a mentor relationship that quickly blossomed into a close friendship.”

Another factor in Watford’s decision had to do with an American Society of Nephrology (ASN) meeting in 2016 “where I was a ‘Kidney STARS’ participant. This program aims to stimulate interest in nephrology among medical students and residents through travel funding to attend the ASN national meeting as well as a multitude of networking opportunities. While attending the meeting in Chicago I met the chief of nephrology, Glenn Chertow, and several other Stanford faculty members during a social event. The combination of that opportunity and my connection with Dimitri spearheaded me coming here.”

Watford met his wife, who was originally from Seattle, at a pre-med summer program at Yale in 2007. She did both undergraduate and medical school at the University of Washington before residency in Miami. For fellowship, “Stanford was on our radar, both because it’s a fabulous training program, and because of the added attraction of being on the West Coast, making it possible to be closer to my wife’s family. Dr. Chertow was very supportive through the whole process of recruiting and has made us truly feel part of a family.”

Once the two friends arrived at Stanford for their fellowships two years apart, they followed different research pathways.

Augustin’s Research Aims
Before Augustin started his fellowship, he was thinking about the intersection of technology and medicine: “I thought there were definitely areas within nephrology that could benefit from technology, but I didn’t have any specific ideas at that time.” He also had interests in interventional nephrology and vascular access for patients who must undergo kidney dialysis several times a week.

While he was a fellow of the Stanford Biodesign Program a few years ago, he says, “I learned about the device innovation process and how it could be used in medicine. One need we started looking into involved problems with hemodialysis fistula maturation.”

Dialysis patients require surgery to create a connection, called a fistula, between their vascular system and the dialysis machine. The surgery connects an artery to a vein, after which the vein dilates and thickens to withstand the blood flow required to send blood through the dialysis machine. There is a period of time following the surgery before the fistula is mature enough to be used for dialysis. That period may last over 90 days.

Methods for determining how mature a fistula is—and how ready it is for dialysis—can include repeated physical exams and at times an ultrasound study. Augustin hopes to find a better way. “During that maturation time,” he explains, “the patient has to use a temporary catheter, and that can be associated with an increased risk for infections and hospitalizations.”

Augustin and his colleagues are in the very early days of designing and creating a wearable device for assessing fistula maturation. With the help of a Kidney Innovation Accelerator (KidneyX) award, they are validating the concept and understanding how the data would be used.

KidneyX is an initiative of the U.S. Department of Health and Human Services and the ASN. The first 15 KidneyX awards are funding different concepts to redesign dialysis. Augustin’s KidneyX Redesign Dialysis Phase 1 prize is helping to fund development and testing of their concept to monitor arteriovenous fistula maturation in real time.

While the road ahead for the device is very long, and it may be many years before it comes before the U.S. Food and Drug Administration for marketing approval, Augustin says that “Fistula maturation is a real problem area that I have an interest in, am dedicated to, and want to make changes in.”

A Focus on Transplant Candidates
On the other hand, Watford’s particular interest comes into play further along the kidney disease process when a patient is in line for a kidney transplant. Northern California has one of the longest kidney transplant wait lists in the country: nine to 10 years for cadaver donation. Given such long waiting periods, during which time the health status of the patients is ever changing, Watford became interested in devising ways to best gauge how well these patients will do both prior to and after transplant. The ultimate goal is to determine a means for providers and transplant programs to ensure the most suitable and medically optimized candidates remain on the transplant list and are offered organs in a time when wait lists are growing ever longer.

The transplant readiness assessment clinic (TRAC) is a novel way for patients to be reassessed for readiness to undergo transplant. TRAC was spearheaded by associate professor Jane Tan, MD, PhD, MS, and clinical assistant professor Xingxing Cheng, MD, MS. As patients move up the wait list toward the one-year point until likely transplant, Watford explains that “we bring them back to TRAC to reassess their physical function. We are using two measurements to assess their readiness: the six-minute walk test and the one-minute sit-to-stand test, with the goal of correlating these measures to outcomes such as removal from wait list or death before transplant as well as some post-transplant outcomes such as rehospitalization and mortality.”

The hope is that these two objective measures will prove useful in determining patients’ readiness for transplant and provide a tool for programs with the longest waiting times to more effectively manage their wait lists.

Should these two fellows achieve their research goals, many patients with kidney disease at Stanford and elsewhere will undoubtedly benefit.

For fellowship, “Stanford was on our radar, both because it’s a fabulous training program, and because of the added attraction of being on the West Coast, making it possible to be closer to my wife’s family. Dr. Chertow was very supportive through the whole process of recruiting and has made us truly feel part of a family.”

Once the two friends arrived at Stanford for their fellowships two years apart, they followed different research pathways.

Augustin’s Research Aims
Before Augustin started his fellowship, he was thinking about the intersection of technology and medicine: “I thought there were definitely areas within nephrology that could benefit from technology, but I didn’t have any specific ideas at that time.” He also had interests in interventional nephrology and vascular access for patients who must undergo kidney dialysis several times a week.

While he was a fellow of the Stanford Biodesign Program a few years ago, he says, “I learned about the device innovation process and how it could be used in medicine. One need we started looking into involved problems with hemodialysis fistula maturation.”

Dialysis patients require surgery to create a connection, called a fistula, between their vascular system and the dialysis machine. The surgery connects an artery to a vein, after which the vein dilates and thickens to withstand the blood flow required to send blood through the dialysis machine. There is a period of time following the surgery before the fistula is mature enough to be used for dialysis. That period may last over 90 days.

Methods for determining how mature a fistula is—and how ready it is for dialysis—can include repeated physical exams and at times an ultrasound study. Augustin hopes to find a better way. “During that maturation time,” he explains, “the patient has to use a temporary catheter, and that can be associated with an increased risk for infections and hospitalizations.”

Augustin and his colleagues are in the very early days of designing and creating a wearable device for assessing fistula maturation. With the help of a Kidney Innovation Accelerator (KidneyX) award, they are validating the concept and understanding how the data would be used.

KidneyX is an initiative of the U.S. Department of Health and Human Services and the ASN. The first 15 KidneyX awards are funding different concepts to redesign dialysis. Augustin’s KidneyX Redesign Dialysis Phase 1 prize is helping to fund development and testing of their concept to monitor arteriovenous fistula maturation in real time.

While the road ahead for the device is very long, and it may be many years before it comes before the U.S. Food and Drug Administration for marketing approval, Augustin says that “Fistula maturation is a real problem area that I have an interest in, am dedicated to, and want to make changes in.”

Soon Baker and Witteles were co-managing close to 20 patients. “There was a need to bring people together around sarcoidosis,” Baker explains. They wanted to “formalize and standardize” their practice.

At first, this included capturing patient information in a database and collecting samples from willing patients to use for future studies. It snowballed from there—cardiac sarcoidosis is a rare form of the disease; it’s more common to see pulmonary problems. So Baker and Witteles started to include pulmonologists (including Rishi Raj, MD, clinical professor of pulmonary and critical care medicine) in their work. From there, it transformed into what is now known as the Stanford Multidisciplinary Sarcoidosis Program, co-directed by Baker, Witteles, and Raj and staffed by Emily Braley, RN. The program began in June 2019, and as the only program of its kind in Northern California, it’s become a hub for sarcoidosis patients.

In many ways, modern medicine is getting more intimate in scope: Think targeted cell-based therapies or interventions tailored to the microbiome. But in another sense, its scope is also getting broader: More and more frequently, doctors from various specialties are realizing how important interdisciplinary care is to fight diseases and care for patients. The immunology and rheumatology division is a perfect illustration of this principle. Among others, both Matt Baker, MD, MS, clinical assistant professor of immunology and rheumatology, and Tamiko Katsumoto, MD, clinical assistant professor of immunology and rheumatology, are working collaboratively with other divisions on research and patient care.

A Hub to Treat Sarcoidosis

Baker “really fell in love with immunology” when he worked in a lab at the National Institutes of Health before attending medical school at Harvard. His path to medicine was unusual: He grew up in a tiny town in Oregon, living in a log house and attending the local high school, where they had classes in “hatchet throwing and log rolling.” He remembers being struck by the role that his father (the town dentist) and the town doctors played. “It was very Rockwellian—seeing them take care of entire families or running down to help when there was an injury at a sporting event,” Baker explains, “so I always had this idea that I would go into medicine.” After internal medicine training, he chose to specialize in rheumatology. “Ten or 20 years ago, many of the other fields within medicine weren’t really focused on the immune system,” Baker says. “But now it’s clearly involved in just about everything. It was, and is, a really exciting time to be in the field.”

His work eventually led him to Stanford, where he’s become one of the go-to doctors on the West Coast for sarcoidosis, a rare disease that can manifest in various ways, including fibrotic lung disease, lymph node enlargement, and life-threatening problems in the heart. Ron Witteles, MD, associate professor of cardiovascular medicine, often referred his sarcoidosis patients with cardiac involvement to Baker. Soon Baker and Witteles were co-managing close to 20 patients. “There was a need to bring people together around sarcoidosis,” Baker explains. They wanted to “formalize and standardize” their practice.

At first, this included capturing patient information in a database and collecting samples from willing patients to use for future studies. It snowballed from there—cardiac sarcoidosis is a rare form of the disease; it’s more common to see pulmonary problems. So Baker and Witteles started to include pulmonologists (including Rishi Raj, MD, clinical professor of pulmonary and critical care medicine) in their work. From there, it transformed into what is now known as the Stanford Multidisciplinary Sarcoidosis Program, co-directed by Baker, Witteles, and Raj and staffed by Emily Braley, RN. The program began in June 2019, and as the only program of its kind in Northern California, it’s become a hub for sarcoidosis patients.

As part of the program, doctors try to coordinate their clinic days so they can see patients together or at least ensure that the patients can see all the different subspecialists they need to in one day. Baker and his colleagues hope to develop their own algorithm and practice guidelines for the diagnosis and management of sarcoidosis.

Baker is also collecting patient samples to investigate specific cell types that might be involved in sarcoidosis pathogenesis, and he’s recruiting for a study to determine the effectiveness of a drug approved for rheumatoid arthritis in sarcoidosis patients.

The far-reaching ambition of the program is a simple one. “A lot of people come from far away,” Baker says, “so we want to make their visits efficient. Our goal is to be able to provide the best collaborative care possible.”

A Working Group for Adverse Events
Katsumoto also preaches the benefits of interdisciplinary work. She always had “a profound love of internal medicine,” and when the time came to choose her specialty, she found herself torn between oncology and immunology and rheumatology. Ultimately she chose immunology and rheumatology, but as she points out, in many ways her career has now come full circle: After years at UC-San Francisco, then Genentech, and now Stanford, her work has resulted in the creation of a new interdisciplinary project: the Immune-Related Toxicity Group.

The idea for this group arose from the growing trend of applying immunology to cancer treatments, and in Katsumoto’s case, the use of checkpoint inhibitors to fight tumors. As Katsumoto explains, “Normally, the immune system is capable of identifying a tumor and mounting a productive response against it. When cancer develops, often the tumor evolves mechanisms of resisting immune attack.” The checkpoint inhibitors administered by doctors then block the resistance mechanism of the tumor, thereby “unleashing the immune system by taking the brakes off” and allowing the immune system to recognize and attack the tumor. Checkpoint inhibitors have generated impressive long-term responses in some patients, but there’s a secondary issue. When you take the brakes off the immune system, it leaves the patient vulnerable to “immune-related adverse events.”

“Sometimes you get collateral damage to your own internal organs,” Katsumoto says. That’s where she and her colleagues in medicine—jokingly referred to as “the cleanup crew”—come in, and how she first got the idea for the group.

Katsumoto realized while treating these adverse events that there were still knowledge gaps, despite the existence of several guidelines. Clinical questions frequently arise, such as how to optimally manage these adverse events, whether it’s safe to restart the checkpoint inhibitor, and whether it’s safe to use checkpoint inhibitors in patients with pre-existing autoimmunity. Katsumoto wondered about creating a working group, akin to a tumor board, that could provide consultative services, a database, and even a biobank for all these adverse events. As Katsumoto puts it, “It became clear that there was a need for us to come together as a larger multidisciplinary group to really discuss these cases and learn from each other.”

The group is still in its infancy, but Katsumoto has identified interested parties from various disciplines (including oncology, dermatology, gastroenterology, pulmonary medicine, endocrinology, nephrology, hepatology, and neurology), and she’s already getting referrals for patients from colleagues. She’s also involved in a large multisite NIH trial seeking to discover whether patients with pre-existing autoimmunity can safely use checkpoint inhibitor therapy. Another major project involves biomarkers: If doctors can discover which biomarkers identify patients who will respond negatively to checkpoint inhibitor therapy, they can identify problems before any therapy is administered.

She’s hoping to convene the group as a resource for doctors in this rapidly changing field. “This could be a springboard for a lot of collaborative research projects,” Katsumoto envisions. She also hopes that identifying “point people” in various divisions can help improve clinical care.

The Immune-Related Toxicity Group is a relatively new idea for Katsumoto, but her goals for the project prove her determination, and her collaborators are just as eager. “The use of checkpoint inhibitor therapy is growing, almost exponentially. More and more medications are getting approved for new indications every day,” Katsumoto says. And that only proves the greater need for collaboration. As Katsumoto asserts, “The field is growing in real time. We need to band together.”

A Working Group for Adverse Events
Katsumoto also preaches the benefits of interdisciplinary work. She always had “a profound love of internal medicine,” and when the time came to choose her specialty, she found herself torn between oncology and immunology and rheumatology. Ultimately she chose immunology and rheumatology, but as she points out, in many ways her career has now come full circle: After years at UC-San Francisco, then Genentech, and now Stanford, her work has resulted in the creation of a new interdisciplinary project: the Immune-Related Toxicity Group.

The idea for this group arose from the growing trend of applying immunology to cancer treatments, and in Katsumoto’s case, the use of checkpoint inhibitors to fight tumors. As Katsumoto explains, “Normally, the immune system is capable of identifying a tumor and mounting a productive response against it. When cancer develops, often the tumor evolves mechanisms of resisting immune attack.” The checkpoint inhibitors administered by doctors then block the resistance mechanism of the tumor, thereby “unleashing the immune system by taking the brakes off” and allowing the immune system to recognize and attack the tumor. Checkpoint inhibitors have generated impressive long-term responses in some patients, but there’s a secondary issue. When you take the brakes off the immune system, it leaves the patient vulnerable to “immune-related adverse events.”

“Sometimes you get collateral damage to your own internal organs,” Katsumoto says. That’s where she and her colleagues in medicine—jokingly referred to as “the cleanup crew”—come in, and how she first got the idea for the group.

Katsumoto realized while treating these adverse events that there were still knowledge gaps, despite the existence of several guidelines. Clinical questions frequently arise, such as how to optimally manage these adverse events, whether it’s safe to restart the checkpoint inhibitor, and whether it’s safe to use checkpoint inhibitors in patients with pre-existing autoimmunity. Katsumoto wondered about creating a working group, akin to a tumor board, that could provide consultative services, a database, and even a biobank for all these adverse events. As Katsumoto puts it, “It became clear that there was a need for us to come together as a larger multidisciplinary group to really discuss these cases and learn from each other.”

The group is still in its infancy, but Katsumoto has identified interested parties from various disciplines (including oncology, dermatology, gastroenterology, pulmonary medicine, endocrinology, nephrology, hepatology, and neurology), and she’s already getting referrals for patients from colleagues. She’s also involved in a large multisite NIH trial seeking to discover whether patients with pre-existing autoimmunity can safely use checkpoint inhibitor therapy. Another major project involves biomarkers: If doctors can discover which biomarkers identify patients who will respond negatively to checkpoint inhibitor therapy, they can identify problems before any therapy is administered.

She’s hoping to convene the group as a resource for doctors in this rapidly changing field. “This could be a springboard for a lot of collaborative research projects,” Katsumoto envisions. She also hopes that identifying “point people” in various divisions can help improve clinical care.

The Immune-Related Toxicity Group is a relatively new idea for Katsumoto, but her goals for the project prove her determination, and her collaborators are just as eager. “The use of checkpoint inhibitor therapy is growing, almost exponentially. More and more medications are getting approved for new indications every day,” Katsumoto says. And that only proves the greater need for collaboration. As Katsumoto asserts, “The field is growing in real time. We need to band together.”