Portal Vein Stenosis: aka The Stent Clot of 2019

If there’s one thing I’ve learned in my 31 years, it’s that we are not given tomorrow. I know we hear that and think it doesn’t apply to us. We close our eyes at night not even slightly doubting that we will ever wake up. We know God has numbered our days, but we assume that the number most definitely won’t run out any time soon.

As many of you know, I grew up with liver disease. I was pretty stable, and a transplant – or even death for that matter – seemed like it was meant for other people. Definitely not me.

Until it was.

Until it was meant for me.

A routine scan in May, 2010 revealed a random tumor, and just like that, I needed a transplant.

One day, my life seemingly hung in the balance when everything was normal just the day before. Two days before, I was having fun on vacation in Disney World with my family.  Little did we know.

I completed a dozen tests in a matter of days, and within two weeks, I was listed for transplant.

There were procedures. There was chemo. There was waiting. Yet somehow, my anxious heart found peace.

Within three months, I received a transplant. A teenage boy died so I could live. It was a surreal feeling that has never been lost on me. I still can’t fully grasp it. My parents’ daughter, my husband’s wife, my sister’s sister, my children’s mother… I’m alive because another parents’ son and siblings’ brother is forever gone. 

I fought through an 8 hour surgery, the ICU, remembering how to walk, breathe, talk, understand. I endured indescribable pain and somehow produced strength that I didn’t even know I had. My need to love drove my need to live, and I took life one day at a time. My family and friends held me up when I was too weak to stand. They built a hedge around me with their prayers, presence, and support, and I’m forever indebted to them.

As I healed, my body turned into an unrecognizable skeleton. Pounds fell off of me like it was nothing. My incision, 50 staples in three directions, reopened and didn’t completely close for eight weeks. Home care nurses and my mom worked diligently to keep it clean and dressed.

I slowly improved. I regained a lot of my life, yet I wouldn’t feel completely normal for at least a year.

Within months of my transplant, my immunocompromised body caught Epstein Barr virus, and I struggled once again. Not too long after, we realized my spleen was absorbing all of my platelets and white blood cells. After a few months of painful procedures to rule out cancer, we scheduled a splenectomy.

My spleen was bigger than a football (huge) and once gone, my blood counts improved. Again, I healed for a week in the hospital. This time, I received all of my nutrients through a feeding tube. My transplant incision had been mostly re-opened, and I was thankful that it healed quicker this time.

While removing my spleen, my surgeon noticed my portal vein had been compromised. A month after the surgery, I had a stent put in to revive the portal vein. It was a simple procedure, and after one night in the hospital, I was home again and doing well. No pain.

Over the next two years, I had sharp pains all over my abdomen, sometimes mild, and other times, enough to drive me to go to the ER. We finally realized that I had a lot of surgical adhesions – nerves trapped in scar tissue.

The only fix for this would be another surgeon and a reconstructive surgery. My transplant surgeon sent me to a plastic surgeon who performed a reverse abdominoplasty with special care to remove any adhesions. The risk of the surgery would be more adhesions, but thankfully I’ve been free of adhesion pain ever since.

That was August, 2013.

The next several years were very uneventful. I had my tonsils removed, I had (and lost) ear tubes. I got allergy shots.  There were several hospitalizations for viruses with my weak immune system, several rounds of antibiotics for many different bacterial infections… All of this was my new normal. But nothing crazy or super shocking until April, 2019.

I woke up one morning a few weeks ago – one day after Easter and two days before Scott and I were to go to NYC on a fun getaway – sure I had appendicitis. I was in too much pain to drive. Scott was already at work, so I called my mom and asked if she could drive me to the ER. She came quickly, and it didn’t take long to see a compassionate doctor in the ER. He evaluated my symptoms and was in agreement that I definitely had a case of appendicitis. He ordered fluids and m0rphine, and I was a lot more comfortable. He suggested that we run a CT scan to evaluate exactly what was going on. Normally I try to avoid CT scans due to unnecessary radiation, but I was in agreement. Awhile after the scan, he came back to my room and said, “Well, your appendix is fine.” My mom and I looked at each other, confused. Then the word “but” left the doctor’s mouth, and my heart immediately sank. “There appears to be some sort of blood clot in your liver.” Time stopped. He said we needed to get me to the main campus of the hospital ASAP where my transplant team could handle whatever was going on.

An ambulance came and drove me to the main hospital. My mom followed behind. Another CT scan showed that my portal vein stent was compromised, so my team booked an angiogram for the next day, Tuesday.

With a MAC (anesthesia), the interventional radiologist came in through my groin and went up my blood vessels to the liver. The portal vein was indeed closing – it was almost completely clogged – and other blood vessels nearby appeared to be a little thin.

My team wanted that same interventional radiologist to repair the issues, and he didn’t have an opening until that Friday. They kept me in the hospital and monitored my liver via almost-daily ultrasounds. I kept busy doing puzzles on my iPad, reading, and coloring in the coloring book my mom got me in the gift shop.

Friday came, and surgery was scheduled. Scott came up to support me. I was prepped and ready to go, and the doctor came in. First, he said he didn’t know if he could do the procedure if I still had contrast in me from Tuesday’s procedure. He ordered an X-Ray and thankfully, the contrast was gone so he said he could proceed.

Next, it’s routine to give consent for a procedure.  You have to hear the risks and then sign a release. The doctor went over the risks of the procedure – bleeding, etc… all the normal risks. I asked if he had done this procedure before, and he said it was a very rare problem to have, so no, he had not done this exact procedure. He was hand-picked by my transplant team though, so I was okay with that. Nervous, but okay. Then he started detailing some negative outcomes from other similar procedures.

I quickly looked at Scott, and we both had fear in our eyes. Then the doctor said that I didn’t have to have the procedure – I could wait until the stent completely closed off and come in on an emergency basis. He said whoever was on call would perform the procedure.

That sounded much scarier to me. I think he could sense our uneasiness, so he said he would give us a minute to discuss. As soon as he left, Scott immediately started praying aloud. Transplant had previously let us know that this was a big problem, and I couldn’t imagine letting it go until it was a life or death emergency with 0 blood flow to my precious, transplanted liver. Scott agreed. We felt that God was leading us to proceed, so we told the doctor that we wanted to go through with it.

They wheeled my bed into the OR, and I kissed Scott and told him I loved him. I thought back to how easy Tuesday’s angiogram was, and I knew I’d be seeing him soon.

Regardless, I was so nervous. I asked the anesthesiologists give me something to calm me down. They gave me Versed while, unknown to me, Scott was calling my parents to update them on the severity of the procedure. They headed up to Cleveland while I was asleep on Propofol.

I woke up in the PACU. I was in pain. I had to pee and I was so thirsty. I wanted to see my husband. The nurse told me I had some bleeding, and that’s why they were monitoring me closely rather than sending me back to the floor. I was supposed to lay on my right side to put pressure on the bleed. I didn’t think much of it. They were still giving me m0rphine for pain, but somehow the pain felt a little worse. I begged the nurse for crushed ice to chew or water with a swab. She kept reminding me that I was NPO because of the bleeding, in case they needed to put me under again. I didn’t care- I felt like I hadn’t had a sip of water in a week. Before long, Scott appeared with my parents. I didn’t even think twice about seeing my parents even though they weren’t there before the surgery. My husband snuck me more ice, and for that I was grateful. I was so happy to have my family.

The nurse came and told me that they were waiting for a bed to open up in the ICU. I was worried – only super sick people go to the ICU. The only other time I was in the ICU was immediately after my transplant!  The nurse told me it was just because of the unexpected bleeding, and it wouldn’t be for long.

Apparently my doctor went in through my side (at my liver) and once done, his tool was supposed to insert some type of plug to close off the blood vessel and prevent bleeding, however, it wasn’t working properly and he was completely unable to close it off. Therefore it bled until it clotted. I had a lot of blood free-floating around my abdomen. My liver was very irritated, and fluid started collecting as well, I would soon found out.

The few-hour-long procedure ended up taking 6 hours.

Once they took me to the ICU, my family went and ate dinner in nearby Little Italy because the ICU wouldn’t allow them to see me again until they got me transferred and assessed. I was highly annoyed. The nurse was redressing some of my lines, and I’m not sure what else she was doing but I just felt like screaming, “LEAVE ME ALONE.” Thankfully, I tried to be nice but I was tired of being looked at, touched, tested, talked to. Thankfully I didn’t remember that the plan was for me to go home the next day because that had obviously changed.

Again, I was so frustrated to be in the ICU. There were bright lights all over. I had 2 IVs, an arterial line, telemetry leads all over my chest, a urinary catheter, oxygen, and a pulse ox probe wrapped around my finger. Was I really in that bad of shape? Once they took my vitals, the doctor updated my med orders, etc., I was worn out. The ICU was pretty firm on only having two visitors at a time. My family returned and I said goodbye to my parents and my husband. I wanted Scott to stay with me so badly, but he was so spent already, and the ICU doesn’t allow overnight visitors.  Everyone promised to come back the next day, and somehow in all of my fear, I fell asleep out of sheer exhaustion. 

The next day, the nurse was gung-ho about the order to remove my urinary catheter. I told her it was a bad idea and that it took me forever to be able to pee after anesthesia. She persisted, and I proved to her that I could not pee on my own. I kept telling her I needed the catheter back, and she did a quick bladder scan on me probably half a dozen times until it showed enough urine in my bladder that I would most definitely have to go to the bathroom. She brought in a fancy “bedside commode,” and I again proved to her that I indeed could not go. I won that battle, and she had the next shift’s nurse put the catheter back in.

I have nothing against young nurses. Heck, I used to be one. My next nurse seemed like a baby in comparison, but she was nice, and I didn’t care. Until she tried to put the catheter back in. She successfully placed it – twice – IN MY V@GINA! If you don’t understand a urinary catheter, it goes in the urethra, which is an entirely different place than a v@gina. If you don’t understand that, take an anatomy class. Catheters aren’t the most comfortable things to be placed, and even on m0rphine I asked her to find another nurse who had done this before to come handle it. I asked the first nurse if she had successfully placed a urinary catheter before, and she told me she had, possibly around 20 times. I assumed she probably meant on the fake person in her school’s simulation lab. The other nurse saved the day and they let me keep my beloved catheter until the next day, Sunday, when they finally allowed me to go back to the transplant floor.

It was funny because I had the exact same room as before the surgery. I had somehow gained a room mate, but I didn’t really care. I was just happy to be back on a regular floor and out of the ICU! No catheter, no arterial line, no large bore IV. I could walk, and I somehow was just more alert.

And, unfortunately, more cognoscent of the pain.

The hospital is a horrible place for sleep. The PCNA comes in all night (okay, every 4 hours) to get your vitals. Nurses come in to hang your fluids or antibiotics at midnight if needed. Lab comes in between 5-6 to draw blood. A resident or two comes in around 6 to see how you are and gather any new info to tell the other doctors. Food services brings breakfast in around 8, and between 9–10, the entire team of doctors – the attending, residents, physicians assistants, even your regular nurse – parade into your room to ask you questions and make a plan for the day. This is your one chance to request any changes in meds or tell them anything that might help them help you. Every single day I told them how bad the pain was and asked, “Are you sure the bleeding should be THIS painful?” And everyday, they reassured me, “Internal bleeding is one of the most painful things there is.” I told them how I felt cut wide open like when I was transplanted, and they reassured me every single day that the pain was normal for what I had going on. I still can’t understand it. I was really in agony. Thank God for m0rphine. But most narcotics make me itchy, so every 4 hours I got 4mg IV m0rphine with an IV dose of Benadryl. What a poor sight I was.

So Sunday, once back on the unit, I was really wanting to take a shower. I had been laying in a gross hospital gown for 2 entire days. My nurse explained that due to the internal bleeding, my hematocrit was really low (7), and it was too low to safely shower. If I fell or got hurt, it could be very serious. My mom suggested that she could wash my hair in the sink if only we had a chair that fit under the sink. My nurse saved the day and found the perfect chair! So I got a washcloth bath courtesy of myself and a blowout courtesy of my dear mama. I felt like a new person!

The days came and went. I was thankful to have the same nurse during the day for 3 days and the same nurse during the night for 3 nights. Transplant told me on Monday that I could go home whenever I could get onto oral pain meds. I knew it wouldn’t be that day or the next, and I told them that. I got ultrasounds most days to check the bleeding and fluid. The volume was slowly going down. My hematocrit was still struggling, so I received a unit of red blood cells. That, with a few bags of IV fluid, really perked me up. I was still in pain, but I felt more like myself.

My hematocrit increased. I took a shower on my own on Tuesday. The pain persisted. I really wanted to go home.

I decided Wednesday was a good day to try to go home but I had the attitude of, if the pain was too bad, we’d simply wait a day.

My team didn’t push for oral meds until they abruptly cancelled the IV m0rphine on Tuesday without so much as a warning. I had an order for 2 oxyc0done every 6 hours, so we switched to that. By evening, the pain caught up with me and my nurse had the doctor on call put in an order for another dose of m0rphine. I was discouraged, really wanting to be on oral meds so I could go home. By the next day, I was fine on the oral oxyc0done. Uncomfortable, but not in severe pain.  Then the physicians assistant told me the maximum she could legally send me home on would be one oxyc0done every six hours – less than half of what I was taking orally in the hospital. I’m not going to get into my opi0id reform rant right now, but that’s a huge jump. She told me I could alternate it with muscle relaxers and Tylenol once I got home, and that made me feel “safer.” I figured, worst case scenario, I could just get re-admitted if the pain was that bad. (Thank God it wasn’t, and I did well resting at home on the oxyc0done, muscle relaxers, and Tylenol, and I’m very proud that I only took the oxyc0done through the weekend and had 1 extra dose on Monday until I was completely off of it.)

That last day in the hospital though, that Wednesday, was hard. I was so exhausted from not sleeping well. I had been on m0rphine for 8 days. I had started wheezing because of all of the fluid in my abdomen. I was receiving breathing treatments for the wheezing and cough I had. (The cough is a very long story – I had it for about a month due to being sick and then allergies…. I still had it in the hospital and even completely lost my voice.  After the surgery though, it became a new, deep, productive cough… it was just a mess.) I had two panic attacks, and my physicians assistant only let me have half the Ativ@n I take at home until I asked to speak to her, broke down in tears, and she agreed to let me take the other half. My poor husband has never seen me as bad off as I was for those 9 days in the hospital. And on that Wednesday, I just sobbed in his arms. I was so overwhelmed, I felt like I was having a little bit of withdrawal from the IV m0rphine, plus I was scared of the pain, a little scared to go home.

They had an ultrasound scheduled for that day, but they were late getting the order in, so my scan didn’t happen until 3pm. I got back to my room around 4, and the scan wasn’t resulted until around 5. It showed the bleeding in a different spot, so the plan was to do a blood test to see if my hematocrit was the same as it was in the morning or if it had dropped. A drop would indicate active, new bleeding. That took an hour to come back, but thankfully, my hematocrit actually increased! So the conclusion was that it was old blood just moving around.

We didn’t get home until around 8ish. I was so excited to see my dogs. Haylie nonchalantly greeted me, and Ruby jumped up on me and squealed in delight. Scott helped me get settled, and I slept until afternoon the next day.

The first few days home, my mom came over while Scott worked. Friday I had an appointment with my PCP and she helped answer some questions and transition me out of being hospitalized. She gave me a prescription for Zofran which I had been taking for nausea, and reassured me that everything was all right.

I rested and rested for the coming days, and I spent the following week (this past week) resting and laying low. My last dose of narc0tic was Monday, and Wednesday was my first day driving again. I had an appointment both Wednesday and Thursday (yesterday) and although I’m pretty sore and weak, I’m only on Tylenol for the pain and am determined to resume my normal life next week.

We’ve been so blessed to receive several meals from people at our church. I don’t have much of an appetite and have been losing weight, but I’m not up to cooking for Scott so it’s been great. We almost have too much food!

Right now I’m still sore and get exhausted by 4pm. I’m slowly getting over the 99* mini-temps and chills I’ve had since the hospital.  I have nausea and an awful appetite and am down just over 10lbs. I think my poor stomach and digestive system are just super confused. My doctors say to give it time.

I had a follow up with my transplant surgeon on Monday. A new scan showed that more bleeding and fluid had been absorbed. There was discussion of blood thinners while I was inpatient, and for now – thankfully – I just have to take a baby aspirin. My labs looked amazing, and everyone was really happy with my progress. I have a follow up scan next Wednesday, and we plan on doing ultrasounds every 6-12 months to make sure this doesn’t happen again.

So, you wonder what caused the stent to be almost completely closed off? “Low dose” hormones I was put on in October for premature ovarian insufficiency, aka “when your body doesn’t make enough estrogen, putting you at risk of heart disease and osteoporosis.” My surgeon told me they were not low dose as the OBGYN had told me. So I’ll deal with that when I visit her in a month.

I also want to add that in the hospital, my sweet friend visited me a couple times and my sister in law came for a great visit one evening before the surgery. The thing about being in Cleveland is that it’s an hour away from most of my friends and family, so that makes visits even more special.  I’m so blessed to have great friends and family. I received so many cards, texts, messages…. I felt all of the prayers and I thank anyone who prayed for me. 

I know this post was long, but my hope is the same as always: that anyone struggling with something similar can either find answers or courage from what I went through. 

This experience had reminded me again that life is fragile, and we are not guaranteed tomorrow. I was lying in the ICU when I was supposed to be having an amazing time in NYC with my husband. What a difference a day makes! I was so afraid to die, and thank God I didn’t.  I couldn’t imagine leaving my husband or my family and friends. I was seriously so afraid I wasn’t going to make it. Maybe it was the anesthesia or the drugs, but it’s scary when you are in really bad shape and are powerless to change anything. 

I have a renewed joy of life and love of each new day. I thank God for putting that in my heart and for reminding me how special this life really is.

Much love to you all.

Stereotypes and prejudices

There aren’t many things that make my blood boil, but any kind of prejudice or stereotype will.  Especially when it’s indirectly targeted at me.

I have been absent from my posting for a little bit due to the crazy busy (but wonderful) holidays and wrapping up my baccalaureate degree in Public Health with a focus of Education and Promotion.  But I need to say something important right now.

I’m in a writing intensive course where we are to write a lengthy paper on a topic relating a health disparity.  Naturally, I chose “Organ transplantation among socially vulnerable adults.” A peer commented on my topic, and he mentioned alcoholism and drug abuse-inflicted liver transplants and ended his piece by saying, “I personally don’t agree there is a large enough disparity, only because many of these people’s conditions are self inflicted.”

First of all, self-inflicted or not, you still treat a patient.  If you were a doctor and someone came into your emergency room after trying to commit suicide, would you save them?  Of course you would.  I understand the limited number of livers available makes this a little bit more of an ethical question, and I will digress for a moment to say UNOS (United Network for Organ Sharing) and transplant centers have extremely stringent rules for listing an alcoholic for a transplant.  If you are an alcoholic and need a liver, you wouldn’t even make the waiting list until they were sure you were sober with a low chance of returning to old ways.

It is very hurtful when someone holds a prejudice towards you or one of your kind – your race, your health status, your financial situation, whatever it may be.  Our instructor in this course has specifically asked to know about anything being said by our peers that is “uncomfortable” to us, so I wrote her an email to say I was more than uncomfortable.  I am just posting this so that all of you know that people dying of liver failure waiting on organs are not a bunch of alcoholics.  The majority (90%) of us have, or had, diseases that we in no way, shape, or form, have/had given to ourselves.

I’m extremely uncomfortable with [my peer’s] reply to my paper topic idea, health disparities affecting access to liver transplants. He ended his post by saying, “I personally don’t agree there is a large enough disparity, only because many of these people’s conditions are self inflicted,” referring to drug and alcohol abuse.
This is a huge myth. I became sick with an autoimmune liver disease at age 5. I was not an alcoholic; my body simply attacked itself. I’ve done research on indications of liver transplantation, and alcoholism/drug abuse account for an extremely relatively small proportion of all transplants. When I was a teenager (before my transplant in 2010 at age 23), I had an emergency room nurse flippantly say, “Why do you have liver disease? You must have been an alcoholic for years!” I was heartbroken as it was the first time if had experienced that prejudice. Not one ounce of alcohol had touched my diseased liver. Ever.

Maybe I’m overreacting, but I am hurt by my peer, a student in the advanced stages of a health degree, no less, being condescending toward patients with liver disease.
I tried to politely respond and tell him the truth so that he could learn from this experience. I hope we all learn something from this. Preconceived stereotypes are extremely hurtful, and we must be extremely cautious never to have them with our patients/clients.
Maybe you don’t believe this myth about liver transplant patients but you think all people with diabetes gave it to themselves by eating junk food, all the people in that neighborhood are drug addicts, or even that another race is just a little less “worthy” than yours.  Well, I would like to firmly propose that no one should say anything negative about anyone unless they have done extensive research and know it to be 100% true, 100% of the time.  Which pretty much would eliminate any stereotypes because none of them meet those criteria.  And if you can somehow outsmart me and find something that meet those criteria, and want to voice your prejudice, don’t.

The Case of the Disappearing Liver Disease

This story from Stanford University School of Medicine is the most personally hopeful account of a medical observation I’ve heard in my lifetime.  As a patient who was forced into a liver transplant due to Primary sclerosing cholangitis and having met friends along the way with identical stories, this article ought to inspire a lot of us.  There is no cure for our disease – none but transplant itself.  But sometimes, by the point a patient is sick enough to get to that point on the list, he or she is too sick for transplant.  Not to mention the ease of a transplant compared with the ease of well… read on and see what this physician noticed is “curing” PSC.  Even though what this doctor at Stanford has discovered perhaps may not necessarily be a medical breakthrough, or not quite yet at this point, it is to us!  To the families this treatment has impacted already, to each patient it’s prevented from transplantation, to each patient whose life it has saved, it most definitely is.

To those of you who may be reading with PSC right now, print this out and take it to your doctor to read over.  I’m sure Dr. Cox would be very interested to know from your physician how your case ended out.  I pray this saves you from a transplant and helps us find a cure so that one day, PSC will only be a term for a disease that used to be.

The Case of the Disappearing Liver Disease
by Erin Digitale; Spring 2011 issue of Stanford Medicine Magazine

IT WAS THE TYPE OF CASE THAT MAKES DOCTORS FEEL HELPLESS.

The 15-year-old boy’s lab tests indicated his liver function was badly impaired. He had a double whammy of two serious gastrointestinal diseases, both lacking cures. On top of it all, his colon was infected with an aggressive bacterial strain, Clostridium difficile.

Although pediatric gastroenterologist Kenneth Cox, MD, had little to offer for the teen’s other problems, he could at least treat the infection. He prescribed the antibiotic vancomycin.

And something very strange happened. The liver-disease symptoms vanished.

“At first I thought it was a coincidence,” says Cox, now chief medical officer at Lucile Packard Children’s Hospital, recalling the moment in 1993 when he saw the first hint of improvement. Maybe he had misattributed symptoms of infection to liver disease, he thought. “But then I stopped the antibiotic, and the liver disease came back, even though the infection was gone.”

So Cox, who is also associate chair of pediatrics and senior associate dean for pediatric and obstetric clinical affairs at the Stanford School of Medicine, gave a second round of vancomycin. Once again, the teenager’s appetite returned, his pain disappeared and his liver tests normalized.

Cox tried vancomycin in a handful of other patients who shared the teen’s liver and colon diagnoses but had never had C. difficile. These kids had been told that their liver disease, primary sclerosing cholangitis, was untreatable. Even a liver transplant was not a guaranteed cure — the disease could recur and destroy a new organ. Yet with vancomycin, the PSC disappeared.

The discovery left Cox in an unusual position. A coincidence — a serendipitous colon infection, of all things — left him holding a potential silver bullet for a devastating and poorly understood pathology.

“The problem is that I’m dealing with a very small group of kids with an unusual disease,” he says. “How do I get the science to prove that vancomycin works, so that all of my colleagues would say, ‘This is the therapy’?”

UNEXPLAINED DESTRUCTION

PSC starts in the “biliary tree,” the tree-shaped network of tubes that carry newly manufactured bile from the liver through the bile duct to the intestine, where bile aids digestion and absorption of dietary fat. In PSC, for reasons no one understands, the tubes become blocked by inflammation. So bile backs up, destroying liver cells and eventually causing cirrhosis.

The rare disease, which occurs in about 10 people of every million, leaves patients feeling severely unwell, with abdominal pain, itching, jaundice, poor appetite, deep fatigue and signs of malnourishment. It can hit people of any age. About three-quarters of PSC patients — including the 15-year-old who started Cox’s research odyssey — also have the more-common diagnosis of inflammatory bowel disease, another poorly understood condition, which is characterized by inflammation and ulceration of the intestine, diarrhea, abdominal pain and a host of other problems.

Cox and his Stanford collaborators believe that if they can figure out how vancomycin alleviates PSC, they’ll solve two mysteries at once. Not only will they have the evidence to convince other physicians that vancomycin is a good PSC treatment, but by finding out how the drug works, they may also learn how PSC begins — which may open doors to better therapies.

Although the research task is daunting, beneath Cox’s caution about its challenges is a definite sense of excitement.

“Most discoveries come by careful observation. I feel lucky that I’ve made this observation,” he says. “The remarkable part is, not only do the liver tests get better, but the children also feel so much better. If you take a look at these children before and after therapy, they don’t look like the same child.”

RESCUING A TODDLER’S LIVER

One of the most dramatic vancomycin-induced transformations came in 2005, after Cox’s team suggested the drug to Lyn Woodward and Melissa Hartman. Their little girl had been through the diagnostic wringer.

Things began to go wrong for Ellery Woodward-Hartman at 8 months of age, when her growth started to lag behind that of her twin brother, Robert. Her liver function gradually worsened; no one could figure out why. By the time she turned 2, Ellery’s liver was scarred with cirrhosis and she was badly jaundiced. Before Cox saw her, other physicians had tested Ellery for everything from cystic fibrosis to lymphoma to HIV. None of those diagnoses fit, and her liver was getting worse. Woodward and Hartman were told to anticipate a liver transplant.

“I thought, this can’t be happening,” Hartman says.

In late October 2005, Cox’s pediatric gastroenterology fellow, Anca Safta, MD, read Ellery’s chart. The symptoms lined up with PSC, Safta and Cox agreed. Safta proposed vancomycin treatment to the family.

“She said, ‘I know about Ellery; we have something that can help her,’” Woodward says, recalling her first conversation with Safta.

“There’s a line from Emily Dickinson: ‘Hope is the thing with feathers,’” Hartman says. “I thought of that poem. It was such a relief.”

 ‘MOST DISCOVERIES COME BY CAREFUL OBSERVATION. I FEEL LUCKY THAT I’VE  MADE THIS OBSERVATION.’Cox wasn’t sure a child as sick as Ellery would benefit from the therapy; his other patients had mostly been at earlier stages of PSC illness. Maybe the antibiotic would at least give her a few months to get stronger before a transplant, he told Woodward and Hartman. Cox wrote the prescription and told the family he would follow up with them soon.

CLUES FROM THE CLINIC

Since 1993, Cox has tried vancomycin on every PSC patient he’s treated, slowly accumulating evidence for the drug’s effects. In 2008, he published clinical observations of the first 14 patients, showing the drug caused improvement in blood markers of liver failure. The index patient, now an adult, is no longer in Cox’s care, but last Cox knew, he continued to do well. To date, 33 of Cox’s patients, plus a handful of others cared for by colleagues around the country, have received the drug. But it’s still largely unknown as a PSC therapy.

Funding has been one obstacle to advancing the research. So far, the work has proceeded without traditional funding sources such as NIH grants. Instead, patients’ families have financed the research via a parent-launched nonprofit, the Children’s PSC Foundation. Cox is now working to secure pharmaceutical company funding for a multicenter study to enable researchers to try the drug in a larger group of adults and children.

The Case of the Disappearing Liver Disease

Bile normally moves from the liver through the branching network of ducts to the intestine, where it digests dietary fat. In primary sclerosing cholangitis, a rare liver disease, inflammation blocks the ducts. As a result, bile backs up, damaging the liver.

FILLING THE KNOWLEDGE GAPS

In spite of the limited resources, Cox has assembled a multidisciplinary team of Stanford collaborators to figure out how vancomycin works. The scientists are starting from one important clue: They know oral vancomycin, the drug formulation Cox uses for PSC, is not absorbed from the intestine. Yet PSC’s trail of destruction starts with inflammation outside the intestine, in the tubes that drain bile from the liver to the gut. The drug must be acting at a distance — but how?

One hypothesis is that PSC arises when pathogenic bacteria in the gut backflow into the bile duct and start a destructive inflammatory response. Normally, everything moves down the duct in one direction, from liver to intestine.

“Essentially, this would be regurgitation of bacteria into the bile drainage system,” says project collaborator David Relman, MD, a professor of infectious diseases and of microbiology and immunology at Stanford.

Another possibility is that bacteria somehow escape from the gut to the blood, then travel through the blood to the bile duct and trigger inflammation.

Under these hypotheses, which Relman’s laboratory is starting to investigate, vancomycin would resolve PSC with its antibiotic action, killing gut bacteria. To determine if that’s happening, the researchers are first taking a census of the bacterial communities in healthy children’s small intestines.

“Almost everything we know so far about the usual gut microbe community is based on adults,” Relman says.

The researchers plan to compare gut microbes in healthy kids to those in PSC patients before and after vancomycin. Their major obstacle — indeed, the reason we know so little about kids’ gut microbes — is the difficulty of sampling the small intestine’s contents. It would be unethical to perform invasive endoscopy on children who have no medical indication for the procedure, so the control samples in Relman’s new study will come from kids receiving endoscopy to investigate non-PSC complaints such as chronic abdominal pain. It’s also challenging to find “control” children who have not received recent courses of antibiotics. “That we know messes with the normal picture,” Relman says.

Still, he is optimistic about the lab’s prospects for cataloguing the gut microbes of kids with and without PSC. If kids with PSC have “different” bacteria before vancomycin treatment and return to a normal bacterial profile with the drug, it would provide strong circumstantial evidence that bacteria initiate PSC. And it would be a good starting point for studies of how the bacteria incite disease.

AN UNEXPECTED MODUS OPERANDI

Another possibility, however, is that in PSC vancomycin is acting as more than an antibiotic. Though textbooks label it a bacteria-killer, the Stanford team suspects vancomycin is also changing patients’ inflammatory response.

Although the idea might seem strange at first, there’s a well-established precedent for antibiotics quieting inflammation. In the last decade, several groups of researchers have demonstrated that, for example, tetracycline’s anti-inflammatory activity contributes to its effectiveness against rheumatoid arthritis, that macrolide antibiotics reduce inflammation in chronic airway disease, and that amoxicillin lowers bowel inflammation in ulcerative colitis.

If vancomycin is acting as an anti-inflammatory in PSC, says Kari Nadeau, MD, PhD, an assistant professor of pediatric immunology and allergy at Stanford, that suggests PSC is a disease of immune function run amok.

Scott Seki of Nadeau’s group already has some enlightening preliminary data. Regulatory T cells, the immune cells that prevent autoimmune disease by tamping down the inflammatory response, exhibit interesting changes during vancomycin treatment, he has found.

Using blood samples drawn before and after vancomycin therapy, Seki showed that the drug doubles PSC patients’ levels of regulatory T cells. Evidence from other autoimmune diseases suggests this change is big enough to cause therapeutically useful drops in inflammation — in other words, it may explain why vancomycin works. Two other experiments in Nadeau’s lab also pointed to regulatory T cells as key players in the vancomycin response. However, this information is still drawn from observations of a very small group of patients, so the team is now working to expand and strengthen their data.

If the findings about the regulatory T cells do turn out to be the PSC linchpin, Nadeau says, “We might infer that some kind of inflammatory process is turned on early in the life of these children that we should move quickly to try to regulate.”

And if the antibacterial effects of vancomycin are key, Relman says, the best approach would be to design a drug that gets rid of PSC-provoking bacteria but acts more selectively. Right now, vancomycin is probably killing beneficial bacteria that have nothing to do with PSC, he adds. “We’d rather not be using a sledgehammer if something more precise and elegant could be devised.”

SURPRISE ENDING

In mid-November 2005, Ellery Woodward-Hartman’s case was presented to the transplant selection committee at Packard Children’s. Though medical records from her pre-vancomycin days clearly pointed toward transplant, the liver-function tests performed after her first 10 days on vancomycin looked promising. The committee decided to re-evaluate her case in December.

A few weeks later, after about a month on vancomycin, Ellery and her family saw their physicians again. “Dr. Safta and Dr. Cox couldn’t believe how well she looked,” Woodward recalls. Ellery’s jaundice had cleared up. Her belly, previously swollen with fluids that accumulated when her liver function was at its worst, had returned to a healthy shape. She was still tiny in comparison with her twin but she was more energetic.

And by the time the transplant committee reconsidered her case, it was clear that the vancomycin was a success. Ellery didn’t need a liver transplant.

“With the degree of disease she had, I was very surprised,” says Safta, now an assistant professor of pediatric gastroenterology at the University of Maryland. Woodward and Hartman feel extremely grateful for the compassionate care Safta provided when Ellery was at her worst, and they still send periodic updates. “It’s just amazing where Ellery has gotten to,” Safta says. “She’s probably the only one with such severity of cirrhosis that has turned the corner like this.”

Now, after more than five years on vancomycin, Ellery is a thriving 7-year-old. Like other patients taking the drug for PSC, she continues to use it without side effects. Though her liver still bears the scars of cirrhosis, and there’s a possibility she may need a transplant at a future date, her liver-function tests are now normal. Her growth has caught up to her brother’s.

“I can’t even calculate what Dr. Cox has been able to do for Ellery,” Woodward says.

Cox sees Ellery’s case as a gratifying success, and he’s encouraged that emerging Stanford science supports the therapy he discovered by accident. This type of discovery is “one of the rewards of being an academic physician,” he says. His collaborators agree. In a project like this, “the patients talk to you through their data,” says Nadeau. “If they’re getting better, that’s what you take as real. That’s what inspires you to go back to the lab and figure out what is happening.”

But there’s one last hurdle: Cox worries that too many patients like Ellery are never offered vancomycin. More than 6,000 people have received liver transplants because of PSC, he says. Though it sounds like a large number, the disease is rare enough that many gastroenterologists never see a case — and so they aren’t reading the literature about new treatment advances. To try to bridge the gap, Cox has partnered with the Children’s PSC Foundation in hopes of helping physicians and patients’ families learn about the treatment.

At a recent foundation fundraiser, he got to meet a few children who had received the therapy from other doctors.

“Kids came up to say it had changed their lives,” Cox says. “They were so thankful. That makes me think this is the right thing to be doing.”

Here it is…

Today is a very special day. 

It’s my 1-year Transplant Anniversary.

12% of us who receive new livers don’t make it to this day, and that in itself is so sobering to me.  I’ve been given a gift and my body has nurtured it to live within.

After what I’ve been through this year, the polarity of the ups and downs, the critical moments I’ve been though, I’m so thankful to have come out alive.  I pray though I’ve been tried through fire, I’ve come forth like gold.

The memories are so strong today.  Waiting for my organ, the surgery and recovery, trying to merge my new and old lives… Often I don’t like my mind to go to these thoughts, but they are a part of my soul.

Today,  I remember sitting at the kitchen table on a summer night, during the waiting period, reading every word in my transplant binder. I can close my eyes and feel each cool saline flush running into my jugular line, the taste of it behind my throat. Then I remember trying to read the lunch menu only to find the words vibrating beyond recognition all because of the high-dose of steroids I was on.  I remember spending two days at the Clinic in an exhilarating whirlwind of exhaustive testing – all to gain UNOS’ approval.   Then there’s the sick feeling I get when I remember leaving my parents and best friend for the last time, not knowing whether or not I would ever see them again.  I cringe to remember a week propped up on pillows, thoughtfully arranged to take away as much pain as possible.  I remember going into a fake diabetes cycle while I was hospitalized after my transplant.  I had to get my blood sugars drawn and usually had to get insulin afterwards.  I was miserable.  I remember great nurses I had during my 3 hospital stays on the transplant unit, like Chrissy, Natasha, and Kat… and a few who are nameless in my memories, but all as much special.  One word: chemo.  I hate reliving Dr. Peter pulling out my drains like snakes coming out of my abdomen.  I can’t even keep up with the ups and downs of my blood counts! The Epstein-Barr virus was a disaster.  I so love Michelle at LabCare.  I can’t stand remembering the pain that no pain pump could control.  I remember going home – so glad to be home but too extremely uncomfortable to be happy about it.

Sigh.

This year, I realized I was stronger than I thought.  I learned God had the final say and everything before that was in His control.  I really, truly suffered – mentally, physically, and emotionally. I watched my family all but break.  I met new friends.  I learned so much.  I pushed myself.  People sacrificed for me.  I grew.  Yes, somehow I grew.

My transplant was a miracle in many ways.  It is first and foremost a beautiful, selfless gift to me from a complete stranger.  I am humble.  I am without words.  I am forever indebted to the family of my donor, whomever, wherever they may be.  On my day of gratitude and celebration, I know they are mourning the one-year anniversary of their son’s accident and death.  That makes this day so bittersweet.  There’s a little dark cloud in my sky that won’t ever go away.  It’s extra dark today.  If only I could know his first name, even if only for my mind’s sake.

It’s so hard to “get” … 

Someone had to die so I could live.

On another note, I’m thankful for this year although I feel a little “at capacity” right now.  I pray God keeps His hand on my life and on my health, and I’m eager to see what comes from here.

Lastly, I owe a thousand “thank yous” to people literally around the world who have shared in this journey.  If you played any part at all – big or small – in my miracle during the past year, please take a thank you for yourself.  I pray I can give back what has been given to me.

So much love,
Amanda

Soon Friday

Friday’s coming so fast – surgery, again.  Being sliced open and left in major pain, again.

Sigh.

Someone asked me if I was scared.

Of what?

Of dying on the table?  No.  Of the pain?  Scared isn’t the right word.  Of staying away from home, sometimes by myself, for a week?  Yes.  Of being woke up each morning at 5 for labs and residents?  Scared, no, but dreading, yes. Of anesthesia?  Quite the opposite.  Of getting out of bed the first time post-op? Absolutely.

About this whole surgery – it’s weird.  The transplant was sudden, phone-call-at-1:30am type of surprising, so I’m having a hard time knowing what to do with a scheduled surgery.  Most of all, I’m wishing it didn’t have to happen.  Although, I really hope it makes me feel better.  All the doctors say it will.  But once you have staples holding your entire abdomen together once, you never want to go there ever again.

Life as a transplant patient is much different that you’d think from the outside.  It’s much different than a pre-transplant patient could ever understand.  I talked to our Team’s psychiatrist about it and asked her if she finds it common that patients – even while prepared and educated pre-op – can never truly comprehend everything their Team tells them about life post-transplant… if they just can’t grasp it all, whether they are avoiding it or just overwhelmed by the amount of information to take in.  She said she’s often thought the same thing.  It’s just the way it goes.  Then you spend your entire post-transplant life hoping you’ll be one of the successes, one of the 85% of liver transplants that make it, God forbid one of the 15%. You do all you can to prevent rejection and infection, spend all your life coordinating meds, side effects, and regular tests to make sure you’re still in the clear.

As you all know, it’s a game of white blood cells lately, and my WBCs hit 0.8 last week. You guessed it, I was on Neupogen injections (again) all weekend.  My labs just keep getting worse, so the surgery needs to happen now.  For those who asked, I’ll be getting blood transfusions to make sure my levels are high enough to get through surgery.  Even my family seems more worried than I am.  While this will be no fun, I don’t think it is a bad thing at all.

Although I thought that about the transplant…

I will never, ever be the same.  I don’t think it’s my fault, but I know it’s my fate, forever my future.

And while so much is unknown, and there are so many questions to ask… to God be the glory.

Note: Contact information added to link column (top right)  No unexpected visitors, please.

A road trip, visitors & a splenectomy

It’s 10pm Wednesday night.

I’m sitting in a wheelchair in the backseat of an ambulance being driven by an attractive EMT.  We’re driving on the highway, under the stars, talking about life, love, roadblocks, choices and pain.

He controls my temperature and the car stereo system while he speaks words far more valuable than the gas in his tank or equipment in his trunk.

I’m excited yet petrified to be going to the Clinic.

Excited because it’s my favorite hospital, excited because my doctors are here, and excited because there’s a chance I will be on the transplant unit, able to see some special familiar faces.

Petrified because this is my last chance for answers on my low WBC and platelets. Scared because the next couple days are critical to the rest of my life.

I’m finding out – once and for all – if I need a splenectomy or not, if I want to deal with the side effects or even what those side effects may even be.

Forget the pneumonia hanging out in my chest… My problems now are much more important than that. Or maybe not – what if the worst – or praise the Lord, best! – is yet to be seen?

Either way,

Psalm 23.2-3
He maketh me to lie down in green pastures: he leadeth me beside the still waters.  He restoreth my soul: he leadeth me in the paths of righteousness for his name’s sake.

Amen.

And thank you for all of the sweet friends who came to see me pretty much all day today.  You are all so precious to me.  Thanks for all the words of prayer and thoughts of kindness coming at me from so many places.

Love love love
Amanda

An update & a prayer request

To all my dear friends who read this,

I just wanted to say hi and give you a quick update.  A few of you have become concerned at the lack of updates, so I figured I’d write a quick note.  And apologize.  🙂  As my previous post (the quote) mentions, the days have been flying by, all together too short!  

I’m so grateful that my recovery has been a bit miraculous, and a great part of that means I’m back to normal life already.  Or at least I was. (More on that later) I’m back nannying full-force and even have a special family for a couple weeks that I’ve really been enjoying being a part of.  Plus, the present holiday season and preparing to restart school in January have both been occupying a lot of my time.  I got my driving and lifting restrictions lifted earlier than expected, and I was enjoying living a full life until I experienced a setback yesterday. Hopefully, it should be over by next Tuesday, but in a world where doctors are obsessed with legally covering themselves, and healthcare personnel rule their patients’ time and lives, who really knows?  I would really appreciate your prayers that this gets worked out and, ultimately, ends as soon as possible.

For anyone interested in transplant meds, I’ve been on Prograf since my transplant.  I started at 1mg 2x/day, then the doctors later prescribed Cellcept 250mg 2x/day on top of that, as well as raising the Prograf to 2mg 2x/day.  I just found out this week that ever since I started the Cellcept, there has been a steady decrease in my weekly labs’ white cell count and platelets.  My doctor is having me stop the Cellcept to see what my labs do, as Cellcept can cause both those drops.  We’re predicting now that we stopped Cellcept, my levels will rise back to normal.   I hope so because Cellcept left me in a constant state of nausea, and I’d love to stop it forever.  As a precaution with stopping the Cellcept though, my doctor upped my Prograf again so now it’s at 2.5mg 2x/day.  I’m convinced Prograf is what’s causing the weird symptoms that I’ve been noticing since I got out of the hospital… things like losing more hair than normal and even breaking out more than normal.  (And normal is pretty much never, so it’s been frustrating!)  I think both are slowly getting better, with the exception of my hair being a complete mess – I think the hair I lost when I did the chemoembolization (which was a minimal amount, thank God) is regrowing in now so I have baby hairs that stick straight up in the winter dryness, and the texture overall is just not what it normally is.  It’s very frustrating to me.  

Also frustrating to me is is the fact that I cannot partake in my one and only unsafe addiction, the tanning bed in wintertime. Apparently, the anti-rejection med (Prograf) and the antibiotic I’m on can make any sun, real or fake, really damaging.  I could get burnt and even get skin cancer much easier now.  I’m beginning the spray tan adventures next week (much more expensive than I thought they’d be!) so I may just have to tell you how that goes.  To have a constant tan, you’d have to go every week, which I am NOT doing.  I paid for 3 visits so it better not turn me orange.  🙂

On another note, my incision has been completely healed for a few weeks now, and I’m still grateful for that every single day.  I’m not having much incisional pain at all anymore, and my energy levels are actually a little higher than pre-transplant.  It’s surprising how I can wake up in the morning and be awake and alert, ready to start a new day.  I’m realizing I used to live in an almost constant state of fatigue.  My doctor told me I’d be surprised to see what life was really like after the surgery, and I’m finding that to be true.  I’m hoping everything will continue to improve as I finish healing.  Everyone says you’re not your your full self until at least a year post-transplant, so I’m excited to see where the road leads…

I’m trying to get a post together for Thanksgiving, so until then… be grateful for every breath you take, every moment you live, every person you meet, every place you go.  And please, give back and give life.

Love,

Amanda