Transplant Immunosuppression on Step 1

Like any workaholic second-year medical student, I'm spending part of the holiday break studying for Step 1 of the boards (the standardized Big Test after the first two years of medical school).  But since it is supposed to be a vacation, I felt justified in studying a more familiar topic, so transplant immunosuppression it is.

Wow.  Everyone says that the textbooks and the exams are ten years behind the times, but it's really striking in a field that changes as fast as transplantation.  Also, the testable facts are based on FDA labeling and the approved indications, which are quite a bit more limited than clinical practice, especially for transplants that are done less commonly.  So, what I've "learned" is:

• Cyclosporine, azathioprine, and OKT3 are commonly used immunosuppressants.
• Cyclosporine is used for kidney, liver, and heart transplants; tacrolimus is used for kidney and liver transplants; everything else is used for kidney transplants only...so lung transplants must not need any immunosuppression at all!
• Daclizumab (Zenapax) is used as an antibody against the IL-2 receptor, even though it's no longer manufactured in the US since Simulect (basiliximab) is now preferred.
• Thymoglobulin, Campath (alemtuzumab), and belatacept don't exist (or rather, knowing them won't help me one bit on the test :-/).

Anyway, pretty obvious defense mechanisms in play with this post!  There's more to worry about than the anachronisms in the transplant immunosuppression section, like how much else there is to study, how out of date it may be (without me knowing it), and how much I'll have to unlearn or get a clue about before actually being able to take care of patients.

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Book Review: Intestinal Failure: Diagnosis, Management, and Transplantation

Intestinal transplantation is probably the most esoteric area of organ transplantation, so learning anything about it can be nearly impossible.  The occasional article or meeting isn't nearly enough to get an overall picture of the field, so I was glad to find a book about it called Intestinal Failure: Diagnosis, Management and Transplantation.

For transplantation, this book has it all.  Surgery, immunosuppression, rejection, infections, evaluation...all the usual topics in organ transplantation are included.  In particular, it discusses the different transplant options--isolated intestinal transplant, liver-intestine transplant, and multivisceral transplant--and describes the differences and indications for each.  Piecing this information together from individual articles isn't nearly as useful, since most of them report on one particular procedure at one center with the conclusion of "look how well it worked!"  There could be more detail on some general aspects of transplantation, such as immunology, but there are many other sources for that information, so this book stays focused on its niche and gives plenty of information to understand its topic.

Even though most people reading about intestinal transplantation have an extensive background (either professionally or personally), the book begins with general information about the gastrointestinal system and intestinal failure, which is great.  If I had to name a weakness, it would be the information on parenteral nutrition, which is pretty limited given how important it is in intestinal failure, and doesn't provide nearly enough detail to understand a PN prescription.  Of course, prescribing PN is a specialty in itself for physicians and for dietitians, so it's understandable if it can't be covered here.  Intestinal and multivisceral transplantation is only an interest for me, not something I deal with personally or professionally, so it's great to find a book that explains it well.

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Nephrology - The Best Transplant Field?

I'm in Philadelphia at the American Society for Nephrology Kidney Week.  For me, it's a busy four days of meetings for their medical student program, the ASN Workforce Committee, and the Nephcure Foundation.  Of course, as a medical student attending a specialty meeting, the ubiquitous question is "What do you want to go into?"  I've been telling people something along the lines of "I want to go into transplantation but not sure about what specialty, since there are a lot of possibilities."  The obvious response, it seems, is that the best field for someone interested in transplant is nephrology!  They make some good points:

• The kidney is the most commonly transplanted solid organ, by a pretty wide margin.  There are just more kidney transplants out there.
• Related to the first point, it's feasible to practice transplant nephrology or kidney transplant surgery full time, while specializing in other organs usually requires more non-transplant-related work.
• The immunology of transplant rejection has been best studied in the kidney, both in the pioneering work and in newer research on donor specific antibodies and antibody mediated rejection.
• Renal disease affects many recipients of nonrenal solid organ transplants, due to some immunosuppressant drugs and damage during the serious illness of organ failure.  Luckily, the hearts, lungs, livers, etc. of transplant patients don't tend to be as uniquely harmed.

Anyway, nephrology deserves at least a few days of intense exploration, so tomorrow at 6:30 AM it begins again.

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St. Louis Children's Hospital

I spent the past couple weeks shadowing/observing at St. Louis Children's Hospital. I'm still not at all clear on the best practices for blogging about clinical experiences, so this post will be pretty short and far from a complete recap. Let's just say that they have the largest pediatric heart and lung transplant programs in the country, and that may have been a motivation for my visit.

For what it's worth, I was really impressed. The physicians there shared a realistic understanding of what transplants can and cannot do.  At the same time, they were innovative in trying new things, in the hope that transplantation can do better.  Families were very engaged and involved, which is a credit to both the families and the staff--the relationship definitely needs effort on both sides.  Finally, they were extremely welcoming when a medical student e-mailed from the middle of nowhere saying "I have an interest in transplantation--can I visit and learn about what you do?"

There's a mural outside the entrance to the Cardiac ICU, and the message made me smile every time I saw it.

Thank you, St. Louis.

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Videos

I'm not a guru of videos by any means, but vacations from school are typically a time to vegetate in front of a screen.  Of course, for this blog, it's all about transplant videos.

From the touching (the story of a young girl's heart transplant at UCLA)...




...to the fascinating (a living donor liver transplant operation at Children's Hospital of Pittsburgh)...




...to the catchy (organ donor awareness from the Department of Health and Human Services).




Enjoy!

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Book Review: Breathless

The history of lung transplantation is inexorably linked to the University of Toronto in the 1980s and the surgeons and medical team there at that time. The first lung transplant was performed in Mississippi in 1967, and patients with end-stage lung disease started receiving successful heart-lung transplants at Stanford and Pittsburgh in the early 1980s, but Toronto developed the procedures of single and double lung transplants as they're done today. The names of Drs. Joel Cooper, Alec Patterson, and Griff Pearson are mentioned most as the pioneers, but another member of this team, Dr. Thomas Todd, has documented the history of lung transplantation firsthand in his book Breathless: A Transplant Surgeon's Journal.

Breathless is almost a Midnight's Children of lung transplantation; when the first lung transplant in Toronto is performed, Dr. Todd is a senior resident still in training, and when the field is mature, Dr. Todd is retiring. In between, he takes on the roles of doctor to many lung transplant patients, donor surgeon traveling the country to procure lungs, a position at another hospital, and finally the director of the thoracic surgery department in Toronto. Compared to many books by physicians, he doesn't focus extensively on the medical details of his experience, but does a great job telling the stories of the hospital environment, the politics, and the patients. Some of the stories are inspiring (the first patient's recovery), some are frustrating (departure of the pioneering surgeons), and some are funny (a patient's question of "Can we have sex?").

One downside of the book is that the author's role was somewhat outside the historical limelight, so it's sometimes challenging to connect the stories he tells with the history of lung transplants as it's usually reported. He also takes some diversions into the non-transplant work of a general thoracic surgery service, but I found these to be interesting as well. Overall, this book provides a very interesting account of the history of lung transplantation and how it became the field it is today.

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Pediatric vs. Adult Transplants

Pediatric transplantation has been a focus of this blog, mainly because I'm especially interested in the stories and unique issues of children who need organ transplants. Many aspects of transplantation are similar between children and adults, but there are some key differences.

Kidney

Percent pediatric: 5%

Indications in adults

• Diabetes
• Hypertension
• Glomerulonephritis

Indications in children

• Renal dysplasia
• Posterior urethral valve
• Focal segmental glomerulosclerosis

Differences in surgical approach

In adults, a kidney transplant is placed in the pelvis and attached to the blood vessels going to the leg (usually the external iliac vessels). For children between 10 kg and 20 kg, the kidney is placed in the abdomen and attached to the main blood vessels in the body (aorta and inferior vena cava). For children under 10 kg, dialysis is generally preferred to a kidney transplant. Young children actually do better with adult kidneys rather than kidneys from other children.

Liver

Percent pediatric: 12%

Indications in adults

• Hepatitis C infection
• Alcoholic cirrhosis
• Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC)

Indications in children

• Biliary atresia
• Metabolic diseases
• Fulminant hepatic failure

Differences in surgical approach

Children can often receive the left lateral lobe of an adult liver, either from a deceased donor (split liver transplant) or a living donor (living donor liver transplant). The left lateral lobe is relatively easier to identify and divide than the right lateral lobe (relatively easier--both are very challenging operations!), and children were the first recipients of partial liver transplants. Children can also receive a whole organ liver transplant from another child.

Heart

Percent pediatric: 13%

Indications in adults

• Ischemic cardiomyopathy
• Idiopathic cardiomyopathy

Indications in children

• Cardiomyopathy (particularly dilated cardiomyopathy)
• Congenital heart disease (particularly hypoplastic left heart syndrome)

Differences in surgical approach

Patients receiving heart transplants for congenital heart diseases (usually children, sometimes adults) often need a longer segment of donor aorta with the transplant. The native aorta may have been part of the original problem and reconstructed as a "neoaorta" as part of the Norwood operation, so the aorta may also need replaced at the time the heart needs replaced.

Lung

Percent pediatric: 4%

Indications in adults

• COPD (chronic obstructive pulmonary disease)
• Cystic fibrosis
• Idiopathic pulmonary fibrosis

Indications in children

• Cystic fibrosis
• Pulmonary hypertension
• Congenital lung malformations

Differences in surgical approach

The younger and smaller a lung transplant patient is, the more likely they are to receive a double lung transplant and need cardiopulmonary (heart-lung) bypass for the operation. However, the operation is generally the same in children and adults.

Small bowel

Percent pediatric: 57%

Indications in adults

• Mesenteric ischemia
• Crohn's disease
• Intestinal tumors (desmoid and carcinoid)

Indications in children

• Gastroschisis
• Necrotizing enterocolitis (NEC)
• Malrotation and midgut volvulus

Differences in surgical approach

One of the challenges with intestinal transplants is that the donor usually needs to be of a smaller body size than the recipient. Since children needing intestinal transplants are small already (because of their intestinal failure and...because they're children), finding a smaller donor than the recipient can be especially challenging.

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