Peutz-jeghers syndrome (PJS) is an inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. Individuals that present with PJS tend to have polyps often in their small intestine as well as their stomach and large intestine. Recently the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) group published the first set of guidelines in treating PJS in pediatric patients.
Hear from Thomas Attard MD, a core contributing author to the ESPGHAN guidelines and Caitlin Lawson, MS, CGC, on how Children’s Mercy manages pediatric patients in view of the new recommendations and how novel techniques available at Children’s Mercy impact patient management and outcomes.
Management and Treatment for Peutz-Jeghers Syndrome
Featured Speaker:
Learn more about Thomas Attard, MD
Caitlin Lawson is a certified genetic counselor and graduated from Northwestern University with a BA in psychology and a MS in genetic counseling. She has been involved with the Hereditary Polyposis program at Children’s Mercy Hospital since 2012.
Thomas Attard, MD & Caitlin Lawson, MS, CGC
Thomas Attard, MD is a pediatric gastroenterologist and medical director for endoscopy services at Children’s Mercy Kansas City. He completed training in Pediatric Gastroenterology at The John Hopkins University School of Medicine including research in Pediatric Hereditary Polyposis in collaboration with The Johns Hopkins Hereditary Polyposis Registry. He subsequently worked in close collaboration with Dr Henry Lynch at the Creighton University Department of Preventive Medicine and hereditary Cancer program. He directs the Pediatric Hereditary Polyposis program at Children’s Mercy Hospital. He is co-author on the recently discussed European Society of Pediatric Gastroenterology (ESPGHAN) guidelines on the management of Hereditary Polyposis Syndromes in Children.Learn more about Thomas Attard, MD
Caitlin Lawson is a certified genetic counselor and graduated from Northwestern University with a BA in psychology and a MS in genetic counseling. She has been involved with the Hereditary Polyposis program at Children’s Mercy Hospital since 2012.
Transcription:
Management and Treatment for Peutz-Jeghers Syndrome
Dr. Michael Smith (Host): So, our topic today is management and treatment for Peutz-Jeghers Syndrome or PJS. My guests are Dr. Thomas Attard and Caitlin Lawson. Dr. Attard is the medical director for the endoscopy services at Children’s Mercy Kansas City, and Caitlin is a certified genetic counsellor. She’s been involved with the hereditary polyposis program at Children’s Mercy Hospital since 2012. Dr. Attard and Caitlin, welcome to the show.
Thomas Attard, MD (Guest): Thank you. Thanks for inviting us.
Caitlin Lawson, MS (Guest): Thank you.
Host: So why don’t we start with you, Dr. Attard, and how about just a nice review of PJS?
Dr. Attard: Thanks. So, thanks for doing this Mike. So PJS is one of the several hereditary polyposis syndromes that we deal with in children. It’s basically an inherited tendency to develop polyps actually throughout the gastrointestinal tract, but even sometimes in the air way and other areas of the body. In the intestinal tract, it carries some significance because those polyps, especially when happening kids, will entail a risk of actually growing to an extent of obstructing the gastrointestinal tract. So those kids, unless identified and treated appropriately, are at risk of having obstruction and repeated surgery.
Later on, in life, the bigger problems are to watch out and screen for malignancy. It is hereditary. So, people need help understanding the genetic cause and pattern of inheritance of it. That’s where we get genetic counselors involved to help the families out with understanding what the long term and the implications towards relatives and siblings are.
Host: Well what a great lead in to a question for Caitlin then. Tell us about your role in helping patients with PJS.
Caitlin: Sure, thanks. So, the genetic counselor in the polyposis clinic attends each of the initial clinic visits. For people who have suspicion or a confirmed diagnosis of Peutz-Jeghers Syndrome, the genetic counselor’s role is reviewing that syndrome and making sure that the family understands that yes, you're in a GI clinic. So, we’re talking about the GI tract. Peutz-Jeghers Syndrome encompasses risks for abnormal cell growth in other parts of the body. So, we review the areas of the body that may be affected by Peutz-Jeghers Syndrome, but most importantly we talk about genetic testing related to this condition.
Peutz-Jeghers Syndrome is caused by mutations in a single gene called STK11. About 95% of patients who have Peutz-Jeghers will have a mutation in that gene if we test the blood. Once we find a mutation, I counsel the family about this, confirm the diagnosis, and who else in the family might also be at risk for Peutz-Jeghers Syndrome. How would we test for it? How long will results take? Will insurance cover it? Is there anything we should put in place before we have testing regarding insurance? Can we be discriminated against if we have a genetic diagnosis in terms of life insurance and health insurance? These are all questions that families ask all the time, and a genetic counselor is specifically trained to help address those.
So, we think about an overview of the condition. We think about access to genetic testing, disseminating results amongst a family, and then discussing reproductive options and risks with patients who are in their later teenage years as well.
Host: Dr. Attard, we now have what is our first set of guidelines for treating PJS. So, tell us a little bit, because I know you were a contributor to this, tell us a little bit about the process for developing these guidelines and how it really came to be.
Dr. Attard: Right. So of course, PJS has been understood for many decades now as a syndrome. There have been several adult based management guidelines or position statements. Guidelines have come from adult gastroenterology societies and genetic societies also. What has been lacking has been an actual effort looking at guidelines focused at the pediatric age range. This is somewhat frustrating, of course, because as we said earlier, although the adults you're looking more in terms of cancer risk and therefore cancer surveillance. In the younger child, cancer risk is not as big of a concern as it is to watch the small intestine and watch out for obstructions. So, questions like how early do you start testing, when do you do genetic testing, what kind of procedures do you do and how often do you do them? What actually is the aim of doing procedures? These were all previously unaddressed.
So, there’s several pediatric gastroenterology societies in the world. They kind of are all unified in one larger team. The European society was the one that actually look on the task at looking at the different syndromes, and of course Peutz-Jeghers was going to be one of them. And come up with a process of finding a certain consensus statement that would guide then the rest of the pediatric GI community it what their decision-making processes would be with regards to these patients.
This was therefore a process that started back in 2012. Four pediatric gastroenterologists— myself who was back then in Europe, Dr. Schlomi who was in Israel, Warren Hyer who was at St. Mark’s, and Carol Durno from Canada—kind of got together and drove the core of this group looking at guidelines. Since then, of course, we’ve had several meetings. Usually at the [inaudible] level. And roped in the expertise of many other individuals. Every single polyposis group, Peutz-Jeghers being one of them, had at least 10 co-authors. All of these individuals were people who were interested in polyposis.
Through a process really of asking single-focused questions, looking at the evidence, discussing the evidence, and then coming up with agreements—or disagreements sometimes—on what needs to be said to the general GI community. We then drove in the creation of these guidelines or position papers which are now submitted for publication.
Host: Yeah. So, Dr. Attard, tell us then how Children’s Mercy is now managing the pediatric patient with PJS in view of these new recommendations. Is it leading to true clinical implementation of these guidelines?
Dr. Attard: Yes, of course. The guidelines have, more than anything, proven at least a validation of what we have done in most scenarios dealing with PJS. To some extent, I don’t really think we’ve changed a lot of our practice. It has, however, made what we do a bit more formally established. Meaning we all knew that there was a risk, for example, of testicular in the kids. We all knew that you had to do regular screening, but we had this ambiguity on well when exactly do you start? Well, now we know. When can you start offering genetic testing? It’s always a debate. Now, at least, we have the support of a consensus statement that has the best evidence. Sometimes not much evidence, but at least the best evidence that is out there giving us a rationale to do what we do.
Specifically, however, in looking at the polyps in the small intestine, what the guidelines have helped us with is actually being able to state that what we’re doing right now endoscopically may seem aggressive. I agree, it totally is, but it is actually the best approach in preventing the significant morbidity of having repeated surgeries that comes after having untreated small intestinal polyps. In essence, what we do when we look for polyps in the small intestine is, we are aggressively pursuing the presence of these polyps using capsule endoscopy. Then when we identify these polyps through capsule endoscopy, then we do after them with what’s called a double balloon enteroscopy, which allows us to remove polyps from the small intestine that we know should we not do that may result in an obstruction, presentation to the emergency room, surgery, resection of the bowel. Even to the extent where you have adults having what’s called Short Bowel Syndrome or intestinal failure should this go uncontrolled. So, in summary, I think it’s provided a validation of a more aggressive approach towards the treatment of PJS patients, even in pediatrics.
Host: Caitlin, how are the guidelines going to effect what you do with genetic counselling?
Caitlin: Yeah. So, kind of veering off of what Dr. Attard said, it’s a lot of validation to practices that we may have already done, but now we have more evidence base to explain why or when an evaluation is necessary. Frequently, the patients who present to us who don’t yet have a confirmed diagnosis may have some features of PJS, but maybe not a completely obvious clinical picture. So, having a guideline to say if you are a certain age and you have some characteristic signs and the absence of a family history or absence of proven PJS types polyps, this is when genetic testing is indicated. This is when it’s appropriate for a young child.
In general, genetic testing in children is treated conservatively for good reasons. Especially when we’re talking about risks of cancer and knowing if they have a predisposition. So, we don’t like to do testing in patients who it’s not warranted for. This helps us give clear guidelines as to how old in the patient in front of us, what features do they have, how suggestive is their history of Peutz-Jeghers Syndrome, and when genetic testing may help clarify the diagnosis.
This condition can be inherited in families, as Dr. Attard has alluded to. It’s an autosomal dominant condition. But a significant portion of patients may represent the very first case in their families. So, they may not have an effected parent. So, we have families who the history seems very obvious. Genetic testing is clearly indicated. But we have very many patients who present to us who have some ambiguity either in their family history or their personal history. So, having guidelines that help us establish what is accepted as standard of care as to when to do genetic evaluation is useful, especially for the patients who have some ambiguity in their history.
It also helps us understand for the patients who asked to say when my other relatives should be tested. So, if we diagnose a patient in our clinic and they have some siblings at home who have not yet shown signs of PJS or not been evaluated for signs of PJS, it helps us give some validation to say why don’t we evaluate your 10-year-old sibling this way and why don’t we evaluate your two-year-old sibling this way. So, it’s a lot of help for us to make things standard of care in this way with guidelines.
Host: Right. Very good. So, it’s formulized what you're doing, it validates what you're doing. So much needed. Dr. Attard and Caitlin, the work that you're doing is amazing to me. I want to thank you for that and I want to thank you for coming on the show today. You're listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you can go to childrensmercy.org. That’s childrensmercy.org. I’m Dr. Mike Smith. Thanks for listening.
Management and Treatment for Peutz-Jeghers Syndrome
Dr. Michael Smith (Host): So, our topic today is management and treatment for Peutz-Jeghers Syndrome or PJS. My guests are Dr. Thomas Attard and Caitlin Lawson. Dr. Attard is the medical director for the endoscopy services at Children’s Mercy Kansas City, and Caitlin is a certified genetic counsellor. She’s been involved with the hereditary polyposis program at Children’s Mercy Hospital since 2012. Dr. Attard and Caitlin, welcome to the show.
Thomas Attard, MD (Guest): Thank you. Thanks for inviting us.
Caitlin Lawson, MS (Guest): Thank you.
Host: So why don’t we start with you, Dr. Attard, and how about just a nice review of PJS?
Dr. Attard: Thanks. So, thanks for doing this Mike. So PJS is one of the several hereditary polyposis syndromes that we deal with in children. It’s basically an inherited tendency to develop polyps actually throughout the gastrointestinal tract, but even sometimes in the air way and other areas of the body. In the intestinal tract, it carries some significance because those polyps, especially when happening kids, will entail a risk of actually growing to an extent of obstructing the gastrointestinal tract. So those kids, unless identified and treated appropriately, are at risk of having obstruction and repeated surgery.
Later on, in life, the bigger problems are to watch out and screen for malignancy. It is hereditary. So, people need help understanding the genetic cause and pattern of inheritance of it. That’s where we get genetic counselors involved to help the families out with understanding what the long term and the implications towards relatives and siblings are.
Host: Well what a great lead in to a question for Caitlin then. Tell us about your role in helping patients with PJS.
Caitlin: Sure, thanks. So, the genetic counselor in the polyposis clinic attends each of the initial clinic visits. For people who have suspicion or a confirmed diagnosis of Peutz-Jeghers Syndrome, the genetic counselor’s role is reviewing that syndrome and making sure that the family understands that yes, you're in a GI clinic. So, we’re talking about the GI tract. Peutz-Jeghers Syndrome encompasses risks for abnormal cell growth in other parts of the body. So, we review the areas of the body that may be affected by Peutz-Jeghers Syndrome, but most importantly we talk about genetic testing related to this condition.
Peutz-Jeghers Syndrome is caused by mutations in a single gene called STK11. About 95% of patients who have Peutz-Jeghers will have a mutation in that gene if we test the blood. Once we find a mutation, I counsel the family about this, confirm the diagnosis, and who else in the family might also be at risk for Peutz-Jeghers Syndrome. How would we test for it? How long will results take? Will insurance cover it? Is there anything we should put in place before we have testing regarding insurance? Can we be discriminated against if we have a genetic diagnosis in terms of life insurance and health insurance? These are all questions that families ask all the time, and a genetic counselor is specifically trained to help address those.
So, we think about an overview of the condition. We think about access to genetic testing, disseminating results amongst a family, and then discussing reproductive options and risks with patients who are in their later teenage years as well.
Host: Dr. Attard, we now have what is our first set of guidelines for treating PJS. So, tell us a little bit, because I know you were a contributor to this, tell us a little bit about the process for developing these guidelines and how it really came to be.
Dr. Attard: Right. So of course, PJS has been understood for many decades now as a syndrome. There have been several adult based management guidelines or position statements. Guidelines have come from adult gastroenterology societies and genetic societies also. What has been lacking has been an actual effort looking at guidelines focused at the pediatric age range. This is somewhat frustrating, of course, because as we said earlier, although the adults you're looking more in terms of cancer risk and therefore cancer surveillance. In the younger child, cancer risk is not as big of a concern as it is to watch the small intestine and watch out for obstructions. So, questions like how early do you start testing, when do you do genetic testing, what kind of procedures do you do and how often do you do them? What actually is the aim of doing procedures? These were all previously unaddressed.
So, there’s several pediatric gastroenterology societies in the world. They kind of are all unified in one larger team. The European society was the one that actually look on the task at looking at the different syndromes, and of course Peutz-Jeghers was going to be one of them. And come up with a process of finding a certain consensus statement that would guide then the rest of the pediatric GI community it what their decision-making processes would be with regards to these patients.
This was therefore a process that started back in 2012. Four pediatric gastroenterologists— myself who was back then in Europe, Dr. Schlomi who was in Israel, Warren Hyer who was at St. Mark’s, and Carol Durno from Canada—kind of got together and drove the core of this group looking at guidelines. Since then, of course, we’ve had several meetings. Usually at the [inaudible] level. And roped in the expertise of many other individuals. Every single polyposis group, Peutz-Jeghers being one of them, had at least 10 co-authors. All of these individuals were people who were interested in polyposis.
Through a process really of asking single-focused questions, looking at the evidence, discussing the evidence, and then coming up with agreements—or disagreements sometimes—on what needs to be said to the general GI community. We then drove in the creation of these guidelines or position papers which are now submitted for publication.
Host: Yeah. So, Dr. Attard, tell us then how Children’s Mercy is now managing the pediatric patient with PJS in view of these new recommendations. Is it leading to true clinical implementation of these guidelines?
Dr. Attard: Yes, of course. The guidelines have, more than anything, proven at least a validation of what we have done in most scenarios dealing with PJS. To some extent, I don’t really think we’ve changed a lot of our practice. It has, however, made what we do a bit more formally established. Meaning we all knew that there was a risk, for example, of testicular in the kids. We all knew that you had to do regular screening, but we had this ambiguity on well when exactly do you start? Well, now we know. When can you start offering genetic testing? It’s always a debate. Now, at least, we have the support of a consensus statement that has the best evidence. Sometimes not much evidence, but at least the best evidence that is out there giving us a rationale to do what we do.
Specifically, however, in looking at the polyps in the small intestine, what the guidelines have helped us with is actually being able to state that what we’re doing right now endoscopically may seem aggressive. I agree, it totally is, but it is actually the best approach in preventing the significant morbidity of having repeated surgeries that comes after having untreated small intestinal polyps. In essence, what we do when we look for polyps in the small intestine is, we are aggressively pursuing the presence of these polyps using capsule endoscopy. Then when we identify these polyps through capsule endoscopy, then we do after them with what’s called a double balloon enteroscopy, which allows us to remove polyps from the small intestine that we know should we not do that may result in an obstruction, presentation to the emergency room, surgery, resection of the bowel. Even to the extent where you have adults having what’s called Short Bowel Syndrome or intestinal failure should this go uncontrolled. So, in summary, I think it’s provided a validation of a more aggressive approach towards the treatment of PJS patients, even in pediatrics.
Host: Caitlin, how are the guidelines going to effect what you do with genetic counselling?
Caitlin: Yeah. So, kind of veering off of what Dr. Attard said, it’s a lot of validation to practices that we may have already done, but now we have more evidence base to explain why or when an evaluation is necessary. Frequently, the patients who present to us who don’t yet have a confirmed diagnosis may have some features of PJS, but maybe not a completely obvious clinical picture. So, having a guideline to say if you are a certain age and you have some characteristic signs and the absence of a family history or absence of proven PJS types polyps, this is when genetic testing is indicated. This is when it’s appropriate for a young child.
In general, genetic testing in children is treated conservatively for good reasons. Especially when we’re talking about risks of cancer and knowing if they have a predisposition. So, we don’t like to do testing in patients who it’s not warranted for. This helps us give clear guidelines as to how old in the patient in front of us, what features do they have, how suggestive is their history of Peutz-Jeghers Syndrome, and when genetic testing may help clarify the diagnosis.
This condition can be inherited in families, as Dr. Attard has alluded to. It’s an autosomal dominant condition. But a significant portion of patients may represent the very first case in their families. So, they may not have an effected parent. So, we have families who the history seems very obvious. Genetic testing is clearly indicated. But we have very many patients who present to us who have some ambiguity either in their family history or their personal history. So, having guidelines that help us establish what is accepted as standard of care as to when to do genetic evaluation is useful, especially for the patients who have some ambiguity in their history.
It also helps us understand for the patients who asked to say when my other relatives should be tested. So, if we diagnose a patient in our clinic and they have some siblings at home who have not yet shown signs of PJS or not been evaluated for signs of PJS, it helps us give some validation to say why don’t we evaluate your 10-year-old sibling this way and why don’t we evaluate your two-year-old sibling this way. So, it’s a lot of help for us to make things standard of care in this way with guidelines.
Host: Right. Very good. So, it’s formulized what you're doing, it validates what you're doing. So much needed. Dr. Attard and Caitlin, the work that you're doing is amazing to me. I want to thank you for that and I want to thank you for coming on the show today. You're listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you can go to childrensmercy.org. That’s childrensmercy.org. I’m Dr. Mike Smith. Thanks for listening.