Protein Associated with Parkinson’s Disease Linked to Human Upper GI Tract Infections

WASHINGTON  —Acute and chronic infections in a person’s upper gastrointestinal tract appear to be linked to Parkinson’s disease, say scientists at Georgetown University Medical Center and their collaborators at the National Institutes of Health and other institutions.

Their study, published in the Journal of Innate Immunity, finds that alpha-Synuclein (αS), the protein implicated in Parkinson’s disease and other forms of neurodegenerative diseases, is released when an infection occurs in the upper GI tract (the esophagus, stomach and duodenum) inducing an immune response as part of the body’s innate immune system. The researchers say that these findings suggest that frequent or chronic upper GI infections could overwhelm the body’s capacity to clear αS, leading to disease.

image-of-brainThis largely federally-funded study helps clarify the function of αS, which is poorly understood, says the study’s senior investigator, Michael Zasloff, MD, PhD, professor of surgery and pediatrics at Georgetown University School of Medicine and scientific director of the MedStar Georgetown Transplant Institute.

This research builds upon prior studies that showed in autopsied material from individuals at very early as well as later stages of Parkinson’s, that the buildup of αS actually begins in the enteric nervous system (nerves in the GI tract). Animal studies have further shown that microbes in the GI tract can induce formation of toxic aggregates in the enteric nervous system, which can then travel up to the brain.

Zasloff and his colleagues studied biopsy samples, collected at the University of Oklahoma Health Sciences Center, from 42 children with upper GI distress. They also looked at another population of 14 MedStar Georgetown University Hospital patients who received an intestinal transplant. This second group had documented cases of infection by Norovirus, a common cause of upper GI infection.

The biopsies showed that expression of αS in enteric nerves of the upper GI tract in these children positively correlated with the degree of acute and chronic inflammation in the intestinal wall. Some highly monitored transplant patients expressed αS as Norovirus was infecting them.

Researchers also showed that human αS could potently attract human immune cells such as macrophages and neutrophils and could “turn on” dendritic cells to alert the immune system of the specific pathogen encountered.

As Zasloff explains, “When expressed in normal amounts following an infection of the upper GI tract, αS is a good molecule. It is protective. The nervous system within the wall of the GI tract detects the presence of a pathogen and responds by releasing αS. αS then attracts white blood cells to the site where it has been released. In addition, αS produced in one nerve can spread to others with which it communicates thereby protecting a large field. By this means, the nervous system can protect both itself as well as the GI tract as a whole in the setting of an infection.”

He adds, “It is well known from animal studies that αS produced in the enteric nervous system can use the nerves connecting the GI tract to the brainstem as an escalator, trafficking αS from the gut to the brain and spreading to centers within the central nervous system.

“But too much αS — such as from multiple or chronic infections — becomes toxic because the system that disposes of αS is overwhelmed, nerves are damaged by the toxic aggregates that form and chronic inflammation ensues. Damage occurs both within the nervous system of the GI tract and the brain.”

Zasloff says the new findings “make sense” of observations made in Parkinson’s disease patients, such as the presence of chronic constipation from damage to the enteric nervous system that develops decades before brain symptoms become apparent and that chronic upper GI distress is relatively common in people who develop Parkinson’s.

Zasloff adds that the publication of this study coincides with the start of a clinical trial targeting the accumulation of αS in the enteric nervous system. The phase 1/2a study is examining the safety, tolerability, pharmacokinetics, and pharmacodynamics of an oral drug, ENT-01, a synthetic version of squalamine, a natural steroid made by the dogfish shark, to relieve constipation associated with Parkinson's disease. Research recently published by Zasloff and collaborators demonstrated that squalamine both reduced the formation of toxic αS clumps and their toxicity, in animal experiments. The clinical trial, being conducted in the US, is sponsored by Enterin, Inc.


The study’s lead author was Ethan Stolzenberg MD, PhD, from the University of Oklahoma and its co-senior author was Denise Barbut, MD, FRCP, Enterin, Inc.

Other scientists contributing to the study include De Yang MD, PhD, Joost J. Oppenheim, MD, and Ad Bax, PhD from the National Institutes of Health, E.Y. Lee, and Gerard C. L. Wong, PhD, from the University of California, Los Angeles. Collaborators from Georgetown are Deborah Berry, PhD, Alexander Kroemer, MD, Supti Sen, Stuart Kaufman, MD, Thomas M. Fishbein, MD, and Brent Harris, MD, PhD.

Zasloff is founder, chairman and CEO of Enterin and Barbut is co-founder of Enterin, president and chief medical officer of the company.

The study was funded by the Intramural Research Program of the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (ZIADK029047), the University of Oklahoma, and UCLA training grants from the National Institute of General Medical Sciences (T32GM008185, T32GM008042).

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A Rise in Young People Diagnosed with Colon Cancer

 

“Sometimes you really have to stand up for yourself and say, ‘no, I want a colonoscopy!’” said Wyatt Smith, a 33-year-old patient with colon cancer.

wyatt and dr. marshall - collageAt age 28, Smith was diagnosed with stage 4 colon cancer that spread to his liver.  He suffered from abdominal pain and irregular bowel movements for two years before he sought help from doctors. One doctor thought Smith had irritable bowel syndrome (IBS) or colitis. Another doctor blamed his symptoms on diet. Later, a colonoscopy exam revealed a tumor at the bottom of Smith’s rectum. It was colorectal cancer (CRC), a condition normally associated with an aging population.

“Cancer was nowhere on my mind. I was dumbfounded!” said Smith.

Colon cancer is the third most common cancer in men and women combined, according to the Centers for Disease Control and Prevention (CDC). The National Cancer Institute’s researchers predict a 90% increase for colon cancer incident rates in young people ages 20- to 34-years-old by 2030, based on patient data from 1975 to 2010. 

Current guidelines call for colon cancer screening to begin at age 50. Many doctors encourage people who are at increased or high risk for colon cancer to get screened earlier.  Patients at high risk include those who have a family history of colon cancer, advanced polyps or a history of IBS.IMG_0387

“When I went to medical school, I was taught that colon cancer is a 50 and older disease, but on any given day more than half of my clinic is filled with patients under the age of 50,” said John Marshall, MD, chief of Hematology and Oncology at MedStar Georgetown, and Wyatt Smith’s current physician. “The lack of early detection has lead to some young people under the age of 50 presenting with more advanced disease.”

According to the Colon Cancer Alliance (CCA), an advocacy group dedicated to prevention, patient support and research, young-onset cancer usually begins in the rectum or in a part of the colon that is located near the rectum. Finding cancer in this area can be difficult without a colonoscopy, which means the cancer would then present at a later stage if patients wait to turn 50 to be screened for colon cancer.

The CCA also estimates that 15-50% of young-onset colon cancer patients suffer from misdiagnoses and unrecognized symptoms, which is one reason Mark Mattar, MD and gastroenterologist at MedStar Georgetown, urges young people to get evaluated if they have symptoms or risk factors. He says performing a diagnostic colonoscopy better determines whether a young patient has IBS, inflammatory bowel disease, celiac disease or cancer.

“The goal of screening is to catch the precancerous polyp before any symptoms,” said Dr. Mattar. “Once you have a tumor, you may have a change in your stool caliber, blood in the stool, weight loss, chills or abdominal pain that does not improve.”

Regardless of age, Dr. Mattar recommends that all patients make a prompt appointment with a gastroenterologist if they experience the following symptoms:

  • Blood in the stool
  • Unintentional weight loss
  • Change in stool caliber
  • Abdominal pain

While Smith’s care team continues to treat his cancer and focus on his quality of life today, he continues to advocate for other young patients.

“Age 50 seems like an arbitrary number,” said Smith, thinking about screening guidelines as he received one of his recent chemo infusions at MedStar Georgetown. ”My advice to young people is to listen to your body and be your own advocate with doctors and insurance.”

IMG_7123Joining Smith’s mission to encourage screening for colon cancer at a younger age is colon cancer survivor Austin Thomas. Dressed in her colon-cancer-blue t-shirt and running shoes, she lead the warm up on stage at the Scope it Out 5K held in D.C. this past March.

“When I had symptoms, it was easy for me to think ‘no pain, no gain,’ but I want young people to know that if you’re not feeling well, your body is telling you something,” said Thomas. “Don’t dismiss your symptoms! As uncomfortable as a rectal exam is, it’s quite simple. Why risk it? Get checked!”

Thomas, a nutrition and fitness enthusiast was diagnosed with stage 4 colon cancer at age 27. Her symptoms included severe stomach pain and intermittent rectal bleeding. Doctors thought she had IBS or a ruptured ovarian cyst. A colonoscopy eventually revealed complete blockage due to a tumor. Other tests showed that the cancer had spread to her liver.

For over a year, Thomas took her chemo drugs for treatment, but she continued to train by biking and swimming as a distraction from her cancer. She ran a half marathon after one infusion goal, and, after her final infusion and having no evidence of the disease (NED), she ran the Army 10-Miler. 

Similarly, Smith refused to let his treatments stop him from working and traveling. Hours after he got the news about the aggressive cancer returning, Smith and his fiancé took off to Rome for a week. He said it was what he needed to escape for a bit. One of his goals is to step foot on every continent.  The couple plans to marry in Cape Cod by the end of the year.IMG_7127

“My only advice is to listen to your body,” Smith emphasized. “If you feel like your symptoms are being dismissed by your doctor, say something!”

Providers suggest getting a second and third opinion to better understand alternative options for care. To help with navigation through colon cancer care, doctors encourage patients to ask the following questions:

  • How much experience do you have treating my type of colon cancer?
  • How will this affect my health insurance?
  • What should I say to my health insurance company?
  • How quickly do we need to decide on treatment?
  • Will this treatment affect my daily activity?
  • What is my cancer’s stage and what does it mean?
  • Should I be thinking about genetic testing?
  • What are my options? Would I be a candidate for a clinical trial?
  • Will I be able to work?
  • Will I be able to have children in the future?

Like many other health conditions, prevention and early detection are key to fighting colon cancer.

“Do whatever you can to stay out of my office!” said Dr. Marshall.

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Pancreatic Disease Program Tackles Tough Tumor

By Emily Turk

Last spring, when 58-year-old Kathy Rusenko began having digestive problems, she thought her discomfort was just the result of a bothersome gallbladder. But when her symptoms persisted, she saw a local gastroenterologist who ordered an imaging test.

The result was inconclusive, but Kathy and her husband, Jack, wisely continued to pursue the problem. Her doctor ordered a second MRI, which revealed the frightening diagnosis: pancreatic cancer. A tumor was partially blocking the bile duct that branched out from the pancreas. By then, her skin had the yellow cast of jaundice, and tests indicated elevated tumor markers in her blood.

Her doctor performed a procedure to open up the duct—and immediately referred her to MedStar Georgetown University Hospital.

Pancreatic Cancer ExpertiseUnger Quote thumbnail

By July, Kathy’s treatment was in the able hands of experts at the unique Pancreatic Disease Program at MedStar Georgetown. This multidisciplinary team of physicians has special training and years of experience treating patients with pancreatic diseases, including cancer. Their level of expertise is unmatched in the region—offering hope to patients with often difficult-to-treat pancreatic tumors.

“Mrs. Rusenko met with each of us,” explains oncologist Brandon Smaglo, MD. The team, which also included surgeon Lynt Johnson, MD, and radiation oncologist Keith Unger, MD, worked in tandem to evaluate her condition. “Together, we made recommendations for next steps. It’s a collaborative approach to care that helps increase the chance for a good result,” says Dr. Smaglo.

Many patients with pancreatic cancer are diagnosed in the late stages of the disease when it has already spread to other organs. “It is often too late for surgery, and this cancer doesn’t respond as well to treatment as other tumors do,” says Dr. Smaglo. “It’s very aggressive.”

Kathy Rusenko
Kathy Rusenko

Beating the Odds

“Only ten percent of patients with pancreatic tumors are candidates for surgery,” Dr. Johnson explains. “And of these people, an even smaller number have good results.” Kathy was one of the lucky few. Dr. Johnson believed he could remove the tumor surgically. But when he performed an initial exploratory procedure, a complication was revealed. The tumor had wrapped itself around a blood vessel, and removing it could prove dangerous.

“We regrouped,” says Dr. Smaglo. “We knew that, to ensure the best result for Mrs. Rusenko, we needed to take another approach.”

Taking the path less followed—and more tailored to each individual—is the future of cancer treatment. “At MedStar Georgetown, because we have so much experience treating this type of cancer, we feel confident about tailoring treatment protocols and trying newer therapies to improve results for our patients,” says Dr. Unger.

The group’s recommendation was a rare approach to the treatment of pancreatic cancer: neoadjuvant therapy (treatment given as a first step before main treatment). They would use chemotherapy and radiation before surgery to shrink the tumor to a manageable size for removal.

It was an unexpected turn of events, but Kathy and Jack Rusenko stayed positive. “My strong faith in God, prayers from friends around the world, and my family saw me through,” says Kathy.

Kathy began a rigorous schedule of chemotherapy and radiation. “The chemotherapy helps to provide systemic control of the cancer,” explains Dr. Smaglo.

On an alternate week, Kathy underwent CyberKnife therapy, which targets radiation directly at the tumor. “The technique, which we have perfected at MedStar Georgetown, allows us to use higher doses for a shorter period of time, while sparing surrounding tissue,” explains Dr. Unger.

“By December, the tumor had shrunk dramatically, and her tumor markers had improved significantly,” Dr. Johnson says. Surgery was the logical next step in Kathy’s months-long treatment process.

Crazy Good Results

During a six-hour surgery, known as the Whipple procedure, Dr. Johnson removed part of Rusenko’s pancreas, the first portion of her small bowel, the bile duct and her gallbladder—then reconnected them.

Following surgery, the tissue removed by Dr. Johnson was examined by a pathologist. The startling result? No evidence of cancer.

“Immediately after the procedure, Dr. Johnson told me that he couldn’t guarantee anything,” says Kathy. “Later, during the first follow-up appointment, I could tell he was excited. Then he said, ‘The results are crazy good!’”

Months later, Kathy’s life has returned to normal. She has completed a round of oral chemotherapy, and additional follow-up imaging shows no evidence of a tumor.

“I can’t praise the doctors, the technicians and the whole medical team enough,” says Kathy. “They were patient with me and Jack, explained everything, every step of the way. What can I say? God—and the doctors at MedStar Georgetown—are an unbeatable team!”

 

Learn More

To find a pancreatic disease specialist or get more information about pancreatic disease, call our scheduling line or request an appointment online.

Phone: 866-731-PANC

Recognized for Expertise in Treatment of Pancreatic Diseases

By Marianne Worley

One of 30 centers in the United States and the only facility in the Washington, D.C. area, MedStar Georgetown University Hospital has been recognized for the care of people with pancreatic diseases by the National Pancreas Foundation (NPF).

NPF_Logo

The NPF is a non-profit organization that awards the designation after rigorous review, recognizing multidisciplinary treatment of the whole person with a focus on the best outcomes and quality of life.

“We are honored to receive the NPF designation,” says Nadim Haddad, MD, chief of Gastroenterology at MedStar Georgetown. “Patients with pancreatic diseases often present with complicated symptoms that require a high level of expertise to correctly diagnose and treat. In addition to meeting clinical and patient experience criteria, designated centers also seek to advance research and raise awareness of pancreatitis and related conditions among community physicians, allied health professionals, patients, families and the general public.

MedStar Georgetown Recognized for Expertise in Treatment of Pancreatic Diseases

 

Washington, D.C. – September 28, 2015 - MedStar Georgetown University Hospital is proud to be one of 30 centers in the United States and the only facility in the Washington, D.C. area, recognized for the care of people with pancreatic diseases by the National Pancreas Foundation. The NPF is a non-profit organization that awards the designation after rigorously reviewing an institution for its focus on multidisciplinary treatment of pancreatitis and treating the “whole person” with a focus on the best possible outcomes and an improved quality of life.

“We are honored to receive the NPF designation and we hope it will help patients suffering with pancreatic disorders find the expertise they need by seeking out NPF centers for their care,” said Nadim Haddad, MD, chief, Gastroenterology at MedStar Georgetown.  “Patients with pancreatic diseases often present with complicated symptoms that require a high level of expertise to correctly diagnose and treat. At MedStar Georgetown we have a comprehensive set of services including the latest technology in pancreatic diagnostics, pain management, the newest treatments for pancreatic cancer, pancreas transplant and now islet cell transplant.”

“The NPF Center designation will help us to better serve this important patient population,” said Matthew Alsante, executive director of the National Pancreas Foundation. “We can recommend with confidence that patients will receive quality care at these designated centers.”

An approved NPF Center has to meet the criteria that were developed by a task force of medical experts and patient advocates. Criteria include having required expert physician specialists like gastroenterologists, pancreas surgeons and interventional radiologists along with patient-focused programs like pain management services, psychosocial support and more. Designated centers also seek to advance research and lead the way for heightened awareness and understanding of pancreatitis and related conditions among community physicians, allied health professionals, patients, families and the general public.

 

About The National Pancreas Foundation

Founded in 1997, the National Pancreas Foundation provides hope for those suffering from pancreatitis and pancreatic cancer through funding cutting-edge research, advocating for new and better therapies and providing support and education for patients, caregivers and healthcare professionals. The NPF is the only foundation dedicated to patients suffering from all forms of pancreas disease. For more information visit: www.pancreasfoundation.org.

 

Meet Dr. Nadim Haddad

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NPF_Logo

First Islet Cell Transplant for Chronic Pancreatitis at MedStar Georgetown is Performed

Virginia Woman ‘Feels Amazing’ without Her Pancreas

(Washington, D.C.) September 3, 2015

“Oh my God, I feel amazing,” said Seana Frost- Barnes, 30, of Warrenton, Virginia. “I can’t believe I lived like I did for so long.” 

Seana & Steven
Seana & Steven

Six months ago, Seana would not have described her health as amazing at all. But after becoming MedStar Georgetown University Hospital’s first person to undergo a pancreatectomy and autologous islet cell transplant for chronic pancreatitis, she has every reason to be excited about her new life without chronic pain and constant trips to the hospital.

Islet Cells
Islet Cells

“Her pancreatitis landed her in the emergency room once or twice a week and she had to be admitted to the hospital one to two times a month,” said transplant surgeon Chirag Desai, MD, surgical director of Islet Cell Transplant program at the MedStar Georgetown Transplant Institute. “Like many chronic pancreatitis patients she suffered with constant severe pain, nausea and vomiting.”

A deformity in the ducts of her pancreas likely caused the condition that Seana began to notice when she was 16. The ducts are supposed to drain enzymes from the pancreas. But if they’re anatomically abnormal or clogged, the enzymes stay trapped in the pancreas and cause consistent damage resulting in chronic inflammation of the pancreas with excruciating pain and other symptoms.

“I always knew something was terribly wrong with me but no one could figure it out. Finally, in 2009, after eight years of not knowing what I had, I got my diagnosis. But that wasn’t before I had been taking a lot of narcotic pain medications and my quality of life was not good, Seana said.”

Seana and Two Snakes
Seana and Two Snakes

An avid equestrian, Seana even had to stop riding and competing on her beloved horse, ‘Two Snakes.’ “As I got sicker I was unable to train. I used to do eventing, which is dressage, show jumping and cross country. But I haven’t been riding consistently and can’t do any jumping anymore.”

As trips to the emergency room became more frequent, Seana and her husband Steven began to explore the option of total pancreatectomy and auto islet cell transplant. That would mean the removal of Seana’s entire pancreas, then using a special technology to remove her islet cells from her pancreas and put those cells back into her body.

“I wanted her to have the transplant about one or two years before now,” said Steven.  “I kept telling her that she couldn’t keep living like she was living.”

“I was sick of being sick. I wasn’t happy, and I wasn’t healthy,” said Seana.

The MedStar Georgetown Transplant Institute began an islet cell transplant program in late 2014. Seana was approved for the procedure shortly thereafter.  

But a few days before her scheduled transplant, Seana suffered the worst pancreatic attack she’d ever had. She was hospitalized for two weeks as her condition became life-threatening and her transplant had to be postponed.

“I really thought I was going to die from that episode. The doctors explained that my attacks would likely get worse.”

Surgery
Surgery

After she recovered, on the morning of May 27, 2015 Seana’s islet cell transplant began. Starting at 8:30am Dr. Desai and his team performed the surgery to remove Seana’s entire diseased pancreas.

Islet Cell Lab
Islet Cell Lab

The pancreas was then taken to a special laboratory recently constructed for cell transplant within MedStar Georgetown.  That’s where islet cell laboratory director Wanxing Cui, MD and his team began the lengthy process of islet isolation, or digesting the pancreas gland to separate islet cells out of the pancreas. This procedure yielded a batch of islet cells which were then injected into Seana’s liver where they immediately began to function as if they were within a healthy pancreas. By 6:30 that evening the islet cell transplant was complete.

“Three months later, she is doing great,” said Khalid Khan, MD, Seana’s gastroenterologist and medical director of the MGTI’s Islet Cell Transplant program. “She is taking no insulin.”

Dr. Khan says that some islet cell transplant patients do end up taking insulin after the procedure but many prefer that to the constant pain and suffering of chronic pancreatitis.

“I was totally excited about being the first person to have this done at Georgetown,” said Seana. I was really interested in the whole process because I knew my case was far from routine. If my situation can be a benchmark to help others, I’m all for that.  I only wish I had done it sooner.  Before my transplant I couldn’t bear the thought of going out to buy a loaf of bread. Today I want to do all kinds of things. I want to go on vacation. I want to live my life, which is now a night and day comparison to the way it was before the transplant.”

“Total pancreatectomy with autologous islet cell transplant is a great procedure for a select group of patients with chronic pancreatitis,” said Dr. Desai. “Maximum benefits can be obtained if the patients are evaluated and operated on at right time. However, due to relative unawareness of the procedure and the facilities that offer it, patients are often delayed in seeing us and that can influence their outcome. Our team of physicians and scientists involved with the islet cell isolation procedure has been involved in this field for quite a few years bringing significant experience to this program.”

Seana’s ultimate goal is to get back on Two Snakes before too long and compete. She has visited him almost every day to tell him they will ride together again. 

Their Wedding Day
Their Wedding Day

“I know it won’t be too long before I can get out riding again. My dream is to participate in the International Horse Show. I’m going to give myself a year or two for that. But I’ll get there. ”

 

 

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Precision Medicine Helps One Woman Beat the Odds

Genetic testing can lead pancreatic cancer patients to  the study of tailored treatment

 

(Washington, D.C.) July 28, 2015 – Susan didn’t have time for pancreatic cancer. Business trips to Asia and sailing adventures in the Mediterranean plus an active family added up to a busy life.

Pancreatic Cancer Patient

Last year after returning from one of her trips to India, Susan sought medical treatment for some gastrointestinal problems. She was shocked when tests revealed pancreatic cancer which turned out to be inoperable.

“I just cried,” said Susan, 64.  “Pancreatic cancer is traditionally a death sentence and mine had spread to my liver and lungs.  I did some reading and discovered that I was facing some very tough odds so I needed to seek out some non-standard treatment options.  In my case, that meant a clinical trial.”

“Susan had genetic testing conducted on her tumor which revealed a key gene mutation.  Because of that finding she was able to enroll in a clinical trial studying a treatment tailored to her tumor type,” said Michael Pishvaian, MD, PhD, Susan’s oncologist who specializes in gastrointestinal cancers at the Georgetown Lombardi Comprehensive Cancer Center at MedStar Georgetown University Hospital.

In June 2014 Susan began the experimental treatment regimen which consisted of an FDA-approved pancreatic cancer chemotherapy every other week.  During the week of her chemo treatments she would also take the drug being studied, called a PARP inhibitor, for seven days. PARP inhibitors diminish the ability of cancer cells to fix the damage caused by chemotherapy.

“The pill Susan has been taking inhibits the cancer DNA from repairing itself and coming back,” said Dr. Pishvaian, the study’s principal investigator.  ”By December 2014 all of her cancerous lesions were shrinking and by March 2015 all of her cancer had disappeared.”

Dr. Pishvaian says there are some serious side effects from the treatment regimen that can be managed with medication.

“In nine months all signs of my cancer were gone,” said Susan. “I didn’t expect them ever to say ‘there’s no evidence of cancer.’ It’s just amazing.  I was shocked, surprised and extremely happy.”

Pancreatic Cancer survivor

“We now know that cancer is like snowflakes,” said John Marshall, MD, chief, Hematology/Oncology at MedStar Georgetown University Hospital and director of Georgetown Lombardi’s The Ruesch Center for the Cure of Gastrointestinal Cancers. “All cancers are different. Now we are starting to be able to measure their variability and tailor the treatments to the makeup of the tumor. But only a minority of patients benefit from precision medicine.  It requires a haystack big enough to find all the right needles. That’s why we are studying our use of genetic testing.  Instead of just saying it’s the right thing to do, we need to show it.”

MedStar Georgetown and a number of other U.S. cancer centers are partnering with Texas-based Caris Life Sciences as part of the Caris Centers of Excellence for Precision Medicine Network  to not only conduct tumor profiling but also to develop guidelines and best practices to improve patient outcomes and access to personalized medicine in the area of oncology. 

“Intellectually we know we need to collaborate with other cancer centers to demonstrate in the next year or two that precision medicine is what’s best for our patients,” said Dr. Marshall, medical director of the Caris network. “Working with Caris to study this will help us to prove the worth of personalized medicine.”

Susan says she has no doubt that she has benefitted from the evolving science of personalized or precision medicine. Knowing her particular cancer’s molecular makeup allowed Dr. Pishvaian to offer her participation in a clinical trial tailored to her tumor.

“While not all patients will have the same outcome, Susan’s case is remarkable,” said Dr. Pishvaian.

“I know I’m here today because I entered this study. I am grateful to be alive and that there was a clinical trial that was right for me,” said Susan. “I take it day by day, one moment at a time. I am happy, healthy and I plan to be here tomorrow.”

 

Learn more - watch NBC4 Washington's Curing Cancer: A News4 Special Report

Abbott Laboratories provides the investigational study drug and additional research funding. Dr. Pishvaian reports having no personal financial interests related to the study.

 

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Preventing Esophageal Cancer: Area Experts Treat Barrett’s Esophagus

By Leslie A. Whitlinger

(Washington, DC) - Ever since a potentially fatal bleeding ulcer blindsided John Freshman a decade ago, the government relations specialist has kept a wary eye on his health. An endoscopy became an integral part of John’s annual checkups, giving his gastroenterologist a close look at his patient’s upper digestive tract and reassuring John that he wouldn’t again become the unwitting victim of his family’s history of digestive disease.

That precaution was especially important since John already had Barrett’s esophagus, also known as Barrett’s disease, an uncommon, precancerous condition in which some of the cells lining the esophagus—the tube that connects the mouth to the stomach—morph into cells normally found only in the intestine.

Prevenitng Esophageal Cancer with Barrett's Esophagus Treatment: John Freshman
MedStar Georgetown’s approach to treating Barrett’s esophagus has dramatically reduced John’s risk of developing life-threatening esophageal cancer.

Physicians aren’t exactly sure what triggers the transformation, but constant irritation from gastroesophageal reflux disease (GERD) tops the list of suspects. Up to 15 percent of people with GERD will develop Barrett’s disease but, without an endoscopy, most will never know it. Barrett’s esophagus itself has no symptoms.

When Barrett’s esophagus is stable, it poses a relatively low risk of turning into esophageal cancer. In many cases, though, Barrett’s rogue cells mutate into a more menacing state called dysplasia, greatly upping the odds. If dysplasia continues its downward path, esophageal cancer is soon only one small step away.

In 2011, John’s annual endoscopy revealed distressing news: his Barrett’s condition had crossed the line from harmless to threatening.

“After 15 years of living with Barrett’s without a problem, all of a sudden I was at great risk of getting the worst form of cancer I know of,” says 69-year-old John. “And I was damned scared. But my gastroenterologist reassured me, saying, ‘I’m sending you to MedStar Georgetown University Hospital and the best, most experienced Barrett’s specialist around—John Carroll, MD.’”

MedStar Georgetown is home to a highly respected Gastroenterology Department that treats the largest volume of patients with Barrett’s esophagus in the region. In 2007, it became the first in the area to adopt the latest treatment for Barrett’s— radiofrequency ablation (RFA)—which has been successfully used on more than 500 patients to date.

“RFA works by using heat to destroy Barrett’s precancerous cells,” explains Dr. Carroll, a gastroenterologist who specializes in endoscopic procedures. “It’s most effective against advanced dysplasia and/or when precancerous cells cover a large portion of the esophagus. Unfortunately for John, he met both criteria, with nearly 75 percent of his esophagus affected.”

A mere week after meeting Dr. Carroll, John began RFA treatment, which typically takes three sessions to burn away all aberrant cells. Performed under full anesthesia, each outpatient procedure lasts about 30 minutes, and is repeated every three months to allow the esophagus to heal between sessions.

Before RFA, doctors could do little more than watch and wait until dysplasia turned cancerous, and then they could act. But with few effective treatments, many patients faced major surgery to remove and then reconstruct all or part of the esophagus. By targeting the earlier dysplasia, RFA actually prevents the development of cancer.

That was certainly John’s experience.

“I can’t begin to tell you how lucky I feel,” he says today. “After four RFA treatments, my esophagus was totally clean and it’s remained that way ever since. Even better, no one expects the dysplasia to come back. Dr. Carroll and MedStar Georgetown were just wonderful. They saved me from a bad cancer. I owe them my life.”

To learn more about our gastroenterology services, call 855-546-0863 for an appointment.

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Marianne Worley
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Patient Contact: 855-546-0863

New Device Treats Cause of Reflux Disease, Not Just Symptoms

LINX Implanted in the Esophagus Stops Reflux, Prevents Barrett's Esophagus, a Cause of Esophageal Cancer

(November 24, 2014) In a first for Washington, D.C., patients with painful and potentially dangerous acid reflux now have a new surgical option that treats the cause of the problem at its source, not just the symptoms.

"What happens in people with Gastroesophageal Reflux Disease (GERD) is the sphincter muscle between the esophagus and the stomach that is supposed to keep food and digestive acids in your stomach, opens when it's not supposed to," said Patrick Jackson, MD, gastrointestinal surgeon at MedStar Georgetown University Hospital. "When that muscle opens, acids in the stomach are allowed to flow back up into the esophagus. The acid causes intense heartburn and can lead to Barrett's esophagus, a known cause of esophageal cancer."

Dr. Jackson is the first surgeon in Washington DC to start implanting a device called the LINX Reflux Management System to keep food and stomach acids where they belong.

"LINX works in a simple and elegant way that works with the body to fix a complex problem that's very common in people," said Dr. Jackson. "The LINX device is a ring of small magnetic discs strung on a titanium wire that forms a ring about two inches in diameter. Once surgically installed around the esophagus, it allows food to pass through the esophagus and into the stomach but won't let food or acids come back up."

The outpatient procedure takes about 90 minutes and is performed under general anesthesia. Dr. Jackson tailors the size of the ring of magnetic beads based on the size of each patient's esophagus.

After the procedure, Dr. Jackson says he encourages patients to eat normally right away. "It's important to get the esophagus moving and working soon after surgery. The tissue of the esophagus will scar around the LINX and secure it into place. And because we're treating the mechanical problem with the esophageal sphincter itself, patients no longer need the medications they had been taking for heartburn."

According to Dr. Jackson, good candidates for LINX are those whose heartburn has responded to proton pump inhibiting (PPI) drugs like Nexium, Protonix or Prilosec.

"Those we do not recommend for the procedure are patients with a hiatal hernia larger than three centimeters, people who need regular MRIs because the device is made of metal and those with a history of stroke or neurological problems. Patients with brain cancer are also not candidates for LINX, said Dr. Jackson."

LINX is an alternative to standard surgery for severe GERD called Nissen Fundoplication. "There are side effects to the Nissen like trouble with swallowing and the inability to vomit," said Dr. Jackson. "The LINX has the same rate of effectiveness without the downsides of the Nissen. The LINX procedure is reversible so a patient can always go back and have a Nissen if they want to."

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Marianne Worley
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GI Docs Use Ancient Treatment for Modern Wave of Drug Resistant and Sometimes Fatal Clostridium Difficile; C. Diff.

Fecal Transplants Cure Patients with Life-Threatening Diarrhea Within One to Two Days

(Washington, D.C.) – A modification of a procedure that’s been around since the 4th century in ancient China is being used to cure the devastating and sometimes fatal Clostridium difficile infection. Also known as C. diff, this bacterium runs amok in the GI tract causing debilitating diarrhea that can last for years.

Each year C. diff kills 14,000 people in the United States and affects as many as 336,000, according to the Centers for Disease Control and Prevention.

“Dangerous cases of C. diff are on the rise and we’re seeing it in younger and younger patients,” said Mark Mattar, MD, Gastroenterologist at MedStar Georgetown University Hospital. “We used to see it mainly in the elderly population of people in nursing homes or hospitals but now we’re seeing it in people who have taken antibiotics for everyday ailments like bronchitis or urinary tract infections.”

To treat C. difficile doctors often use antibiotics like Flagyl, or if that doesn’t work, they turn to the stronger vancomycin or even a pricier Dificid antibiotic.  But as its name “difficile” suggests, sometimes even the strongest bacteria killers don’t vanquish C. diff.

That’s when gastroenterologists like Dr. Mattar are trying something old and a little, well, gross and are getting success rates of over 90 percent.

“It’s not hi-tech or glamorous, but we’re transplanting feces from one person to another and within a day or two, their diarrhea is gone,” said Dr. Mattar.

How does it work?“There are trillions of bacteria in the gut, which starts at the mouth and ends at the anus,” explained Dr. Mattar. “Those bacteria live in a delicately balanced world where the flora have to exist in harmony for the GI tract to work properly.  When you take an antibiotic to kill an infection elsewhere in your body, unfortunately you also kill some healthy bacteria in your GI tract and upset that balance. That’s when C. difficile can invade and wreak havoc.”

Camilla Schlegel of Maryland came to see Dr. Mattar recently when her 92 year old mother’s case of C. diff had dragged on for more than 10 months and became life-threatening.  “It was very debilitating and very hard to manage and keep my mother clean,” said Camilla. “My mother was hospitalized for dehydration and various trials of antibiotics. She lost weight and was so weak that she could no longer push herself around in her wheel chair.”

After all else failed, Camilla came to see Dr. Mattar and became a fecal donor for her mother. “At first it sounded off the wall,” Camilla reflected. “But this procedure helped my mother like no other pharmaceutical method did. I was very amazed how quickly it worked. She was feeling better the same day.  She’s been able to eat and propel herself in her wheelchair.”

An intimate partner, housemate, or family member usually works the best for a fecal transplant, also known as fecal microbiota transplantation, or FMT, according to Dr. Mattar.

“I know people might feel squeamish about this procedure,” said Camilla. “But the oddness and inconvenience are minimal in comparison to watching someone you love be so ill and so contagious to others. And there were no side effects here. I call that an all-around win.”

“Our protocol at MedStar Georgetown is to first test the donor for C. diff, GI parasites and other infectious diseases with stool samples and blood tests,” said Dr. Mattar. “Once the donor is deemed appropriate, they’re sent home with a kit with specific instructions to collect and prepare the stool.”

When they return, Dr. Mattar uses colonoscopy to instill the donor feces into the GI tract of the recipient where the donor feces help to restore the normal flora to the GI tract.

“I wish we had done this transplant sooner. In addition to my mother being uncomfortable for so long, there were financial consequences. I had to spend my mother’s dwindling funds to hire extra nursing aides to keep her clean and comfortable. Plus the last medication we tried was $3500 per course and we did three courses.”

“And if the fecal transplant doesn’t work, we can try giving vancomycin again,” said Dr. Mattar. “Studies suggest that the fecal transplant often changes the GI flora enough to make C. difficile susceptible to vancomycin in up to 80 percent of people who were previously resistant to this.”

In Dr. Mattar’s capacity at MedStar Georgetown’s Inflammatory Bowel Disease (IBD) Center, he is also interested in the possible role of FMT to combat inflammatory bowel diseases like ulcerative colitis and Crohn’s disease. “We’re not there yet, but there are small trials revealing that such a shift in the gut microbiome makeup may be helpful in treating IBD. It is thought that IBD comes from an inappropriate immune response towards the gut bacteria. No specific bacterium has been found to be the culprit but it might be related to reduced diversity of these bacteria in patients with IBD. FMT helps bring back the healthy, diverse bacterial flora that can, in turn, decrease the frequency and severity of IBD flares. More studies are needed to establish the safety and efficacy of using FMT in IBD patients.”

“It’s exciting to take old medicine and apply it to the here and now. East meets West; a prime example of integrative medicine that is saving peoples’ lives,” said Dr. Mattar.

The Food and Drug Administration (FDA) has recently taken interest in somehow regulating the administration of FMT. After meetings with the American Gastroenterological Association (AGA) and other prominent organizations, it has been decided that this procedure may be performed for recurrent C. difficile infections when the physician deems it appropriate, with the proper documentation and consent from the patient. Dr. Mattar states, “I've taken it upon myself to keep communication with FDA representatives open about our protocol. The FDA continues to support our efforts as we collaborate with them as an academic center in providing the best care to our patients. We continue to perform these procedures with full support from the FDA.”

Elizabeth Phillips (left) now fully recovered from C. diff, a serious digestive disorder, enjoys a visit from her daughter, Camilla Phillips Schlegel, and Annie, who enjoys Elizabeth's hugs.
Elizabeth Phillips (left) now fully recovered from C. diff, a serious digestive disorder, enjoys a visit from her daughter, Camilla Phillips Schlegel, and Annie, who enjoys Elizabeth's hugs.

About MedStar Georgetown University Hospital

MedStar Georgetown University Hospital is a not-for-profit, acute-care teaching and research hospital with 609 beds located in Northwest Washington, D.C. Founded in the Jesuit principle of cura personalis—caring for the whole person—MedStar Georgetown is committed to offering a variety of innovative diagnostic and treatment options within a trusting and compassionate environment.

MedStar Georgetown’s centers of excellence include neurosciences, transplant, cancer and gastroenterology. Along with Magnet® nurses, internationally recognized physicians, advanced research and cutting-edge technologies, MedStar Georgetown’s healthcare professionals have a reputation for medical excellence and leadership. MedStar Georgetown University Hospital—Knowledge and Compassion Focused on You.

About MedStar Health

MedStar Health combines the best aspects of academic medicine, research and innovation with a complete spectrum of clinical services to advance patient care. As the largest healthcare provider in Maryland and the Washington, D.C., region, MedStar’s 10 hospitals, the MedStar Health Research Institute and a comprehensive scope of health-related organizations are recognized regionally and nationally for excellence in medical care. MedStar has one of the largest graduate medical education programs in the country, training more than 1,100 medical residents annually, and is the medical education and clinical partner of Georgetown University. MedStar Health is a $4.5 billion not-for-profit, regional healthcare system based in Columbia, Maryland, and one of the largest employers in the region. Its almost 30,000 associates and 6,000 affiliated physicians all support MedStar Health’s Patient First philosophy that combines care, compassion and clinical excellence with an emphasis on customer service.

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