So I married a mutant

Well, I can now end my self-imposed silence. To avoid spilling the beans in such a public forum as the internet, I intentionally did not post the information found here: http://link.springer.com/article/10.1007%2Fs00109-014-1205-7#page-1 until it had been properly vetted. Dr. Pacak has been awesome. From a caregiver standpoint, I couldn’t ask for a better “mad scientist” in our corner. He has tirelessly kept us abreast of his research as it related to Lori’s unique issues. Our hope is that someone out there reads this and asks questions of their doctor if they feel something “just isn’t right”. Time and time again, we visited countless doctors who just dismissed Loris condition as “in her head” or a myriad of other reasons why she could not have a pheo and polycythemia at the same time. “…it just isn’t possible” or, “even if you do have it, it is so rare, no one has any idea how to treat you, so don’t come back and see me, because I can’t help you. (All she wanted was a hematologist to prescribe a phlebotomy)

What makes this discovery groundbreaking, is how polycythemia relates to pheos and vice versa. I won’t take the experts out of the paper and attempt to simplify it but do recommend you read it. Below is how it affects us

First, you must understand on a basic level that almost all cancer tumors crave blood and sugar. Since they are our own cells mutated with little self-regulated growth, the better the blood supply and higher levels of sugar they get, the faster and more aggressive they can grow, depending on the genetic mutation. Pheochromocytomas and parganglianomas are different from other more well-known cancers such as lung cancer. The bottom line is, pheos and paras do not respond well to the traditional cancer treatments (CVD chemo, radiation, etc.). The best course of action is the surgical removal of the tumors. With metastatic disease however, sometimes that is not possible due to the location, size, or number of tumors involved.

The best treatment plan is controlling the symptoms of the tumor burden via medication primarily; but diet and other outside factors can play an important part. For Lori, one of those outside factors had always been her getting a phlebotomy. When she wasn’t getting regular phlebotomies, her pheo symptoms increased and her medication just seemed to be less effective. We now know those are the times her tumors were growing and producing catecholamines at a faster rate. Until we were able to find a hematologist willing to prescribe a phlebotomy, managing Lori’s blood was impossible. As mentioned in previous posts, Lori’s tumors were described as “stable”. Since she has not been scanned recently (longer than 6 months), I hold out hope that is still the case. The best treatment plan for her is the management of her blood counts as a way to “control” her tumor burden. Generally speaking, the week after her phlebotomy, is when she feels the best. Pheo symptoms lessen and hypertensive events become less frequent. She has modified her diet and tried to stay away from as many known catecholamine producing foods as she can (within reason and an occasional exception).

Now that this paper has been published, It is our hope that others out there with a polycythemia diagnosis who are JAK2 negative can have an easier time getting answers and results. Since we first started this odyssey, we have met some fantastic individuals both in person and on the web via the Pheochromocytoma and Paraganglianoma Support group on Facebook. The easiest way to find the right group is to type pheo in the Facebook search bar. The first group that shows up should be us. there are other groups, but this one is the most active and has people involved around the world so no matter when you have a question, chances are someone is online and can point you in the right direction.  When we first joined, there were approximately 600 members. Today there are 1300. In a few short years, more and more people are finding out about these diseases and why they used to be called the “great mimic”. I also can not overlook the pheoparatroopers found here: http://www.pheoparatroopers.org/. One of the results of the SPHD1 mutation is to cause a pseudo-hypoxia condition that allows for tumor growth. This is known as a tumor suppressor gene. SDHx is a more common tumor suppressing gene among pheo patients. Another pair of tumor suppressing genes getting a lot of press this month are the BRCA1 and BRCA2. They are 2 of the more common hereditary mutations for breast cancer. PHD1 and PHD2 are also hereditary (that is what germ-line mutation means) and can be passed down. Since there aren’t enough months in the year for all the different cancers out there, I feel October should be known as cancer awareness month; not just breast cancer awareness month.

As much as all the cancers out there are different from each other, they all benefit from research and breakthroughs made on each other. My point to this diatribe is NIH funding must continue. Not only can we not afford to cut cancer, and other rare disease research being performed there; but we need to find ways to increase it. Future generations depend on it even if they don’t know it yet.

Please let your members of Congress know they must not cut the NIH budget.

Thanksgiving 2013

It has been almost a year since I last posted here... The biggest reason why I haven't is quite simply Time. My time this last year seems to have gone by so much faster than than the years before it.

Well, since the weather has turned cold and snowy, I have no more excuses not to make a post. This past year has been exciting in a lot of ways and exhausting in others. I got married officially to Lori at the beginning of this month. Planning that, is a credit to her and her cooking skills, since we tried to keep our expenses under 1K.. We didn't quite make it, but it was worth it. We planned it as a surprise wedding for my family because it is so hard to get all my globe trotting siblings in one place. They were already going to be in town for my cousins wedding, and we did not want to impose on their day. We also did not want my family to plan for the added stress of having 2 weddings in 2 days, so we did not tell anyone. Lori and I planned out the food, Lori cooked it all summer long, and froze it so all we had to do is re-heat it. It went off a little later than planned but all in all, it was a great day. I'm happy I married the most unique person on the planet.

We also have had some good news with our journey. Lori and I now know more about the relationship between Lori's pheochromocytoma/paraganglioma and polycythemia. I can't get specific with the science just yet, as I have been sworn to secrecy. I can say that Lori's tumors are still stable as opposed to being aggressive. In terms of treatment, there is none just yet, but with this type of cancer, you have to know the Why and the How of the symptoms/tumors before you can know the How and What of the treatment.

Most of this year has been spent in one four places; work, home, the car, and lastly, doctor offices.

The first three are pretty normal for most people, the fourth is not. Last year we put over 7500+ miles on our little Kia Rio5 just in doctor visits. This year, while we haven't totaled it up yet, has to be more. More trips to NIH, and more trips to the Cleveland Clinic means so much less time for all the other important things in life.

Lori finally got her surgical hernia and the complex regional pain syndrome taken care of so that was a relief. Both her thumbs now work as they should. Now if we could get Lori's bone pain under control so she can have a better outlook on the day to day grind of being a patient. But we will take that one day at a time just as we have everything else.

My job requires patience, sometimes extreme patience, but in context of dealing with the medical establishment and the lack of overall knowledge about pheo/para within the general population of the medical community; my job is a cakewalk. To say I have generated a mistrust and a bullshit detector for doctors in general, would be an understatement. Not all doctors fit into this, but I have a high standard that very few meet. I have generated my opinion as a result of this journey and my perception is my reality but since this was meant to be a positive post this close to Thanksgiving, I'll stop the negativity here.

I am thankful for another year with my now new bride, Lori. I'm thankful for my family (hers and mine, and the few days we were almost all together). I'm also thankful for all the new people that we have met as a result of this disease. Especially those on the Facebook group, NIH and now tonight, a local couple. My job most definitely. The three people I interact with at work the most have to put up with my “two cents worth” on a daily basis. That in and of itself is priceless to me.

I wish you all a healthy, happy, safe holiday season.

Time

Time waits for no man or woman for that matter......

Its been a long time since I have posted anything on here for many reasons. Some of which I want to address. Not being the cancer patient myself, I don't get to look death straight in the eye, thumb my nose, flip the middle finger at it, and go on about my day. I only get a front row seat to watch the show as the person closest to me gets up day after day and refuses to back down from what life has thrown her way. Lori has struggled with the prognosis that this cancer doesn't fit into any of the “nice” cancers that get the headlines and the research that develop treatment plans. Every type of cancer is different and each robs the body of life in a different way. I have come to realize it doesn't matter though, the end result of death is still the same. It comes for us all, but some see it a little quicker than others. That said, its what you do with the time you have that can sometimes make the difference. Or at least that's what popular culture tells you. It's a lot harder to put into practice from the words you tell yourself in your head and to others when they ask “how are you doing” Patience is a virtue for a reason. As I have gotten older I have come to realize my parents were right about a great many things, the preceding sentence being one of them. Yes I've heard the jokes about what we think of our parents at various ages.. I think we laugh because they are more true than we like to admit. When we are young we say to ourselves “I'm not going to do that when I get old” or “I sure hope..........”. You get the idea.

My point to all this is when we are young, we are full of hope and ideas of how things will be different when we are at whatever age we haven't reached yet. At each stage of life as our goals, hopes and dreams change, the one constant seems to be time. Either its “I can't wait till....” or “there never seems to be enough time for..........”.

The support group Lori and I are in on Facebook for pheochromocytoma/ paraganglianoma has over the last 3 months lost several people. Some have been in the group longer than Lori and I and others not so long. Lori found this group about a year ago when she was at wits end trying to understand why it is so difficult to get a straight answer out of various doctors. It gave us hope and support that we are not alone in this fight, and there are others going through the same bullshit day after day. I feel lucky, guilty and scared at the same time because so far, Lori has beaten the odds to this point. Guilty because some people aren't blessed with the same time. People younger than Lori and I with kids and families that were dead within a year of their diagnosis, even though they got the best treatments money could buy, discovered it “just in time...” Those little buggers released all those chemicals, the body goes into a hypertensive crisis and the person slips into a coma, and all the people left behind have to wait. Wait for a better day. Wait until they can see their loved one again. Wait until they don't feel guilty for the things they never got to say. Wait until the guilt goes away for not being able to do the stuff they wanted, with the person they are closest to. Various books I have read have made the point that waiting for something can be difficult and learning to deal with the time in between can be difficult. Here we are back at time and patience again... See I told you my parents were right.

I used to think I was a strong person but I have realized my parents and siblings were correct all those years ago when they told me I am stubborn. I freely admit that yes I am stubborn, but now I have learned patience. I also have a new admiration for people who have to fight this battle. This lesson that other people might just be battling something harder/ different than the daily trials and tribulations of most peoples lives is not new to me. I was first exposed to the different difficulties of others by my parents at a very young age and it has shaped who I am today, but the fight with this disease will change me in a way that other obstacles I have overcome in my past could not. The difference is I get to watch someone I love fight a battle in which my role is primarily support instead of the person doing the fighting. Now, those that know me, and who I am, may have an idea about what I'm talking about here but most likely you only know various parts of the story.... My history and how I got to be me, will be a later post.

Lori in her own words

Lori is a much better writer than me. She is always a deep thinker I have been pushing her to make her own blog. Well today she finally did it. You may not always agree with what she has to say but she will definately make you do one of the following things with everything she writes: think, laugh,cry or swear at your computer screeen.

Her page can be found in the links section “A Peek into Me" or by going to http://skeletonsinahousewithnoclosets.blogspot.com/

New genetic mutations discovered!!!

Hello All.

It has been a while since my last post. What can I say, it has been a very busy summer. Family birthdays, reunions, wearing multiple hats at work, all make time fly by. I'm updating this blog to share some information that may as yet hold some promise for Lori's unique case. On my links page there is now a link to a new article published in the New England Journal of Medicine called Somatic HIF2A Gain-of-Function Mutations in Paraganglioma with Polycythemia. I have read the entire article and it makes for some very scientific reading. There is a table located in the article that lists the symptoms of the 2 patients with the newly discovered mutation. I have included some of the symptoms listed, the two patients included in the study and Lori's symptoms and how they match up. It is my belief this is the mutation Dr Pacak thought Lori might have when we first went to NIH in April. Since UH hospitals have yet to provide NIH with any unstained tumor blocks for genetic testing, we may not know for sure if Lori has this mutation or not. In part of the article it mentions how the mutations were isolated. Unfortunately the only way is with genetic samples of the actual tumors since the mutation was not not found in DNA from samples of normal tissue. Thanks again UH.

	Patient 1	Patient 2	Lori
Age at onset of diagnosed condition
Polycythemia	At birth	At birth	6yr
Multiple paragangliomas	14yr	18yr	47yr
Multiple somatostatinomas	29 yr	No	No
Recurrent paragangliomas on imaging	Yes	No	yes
Metastatic tumors on imaging No No	No	No	yes
Age at onset of clinical characteristics
Abnormal redness of the body	8yr	At birth	As long as she can remember
Blue feet No	No	1yr	No
Red cheeks and lips	8yr	At birth	yes
Growth or developmental abnormalities	No	No	No
Marfanoid habitus, gothic palate, arachnodactyly	Yes	No	No
Cardiac systolic murmur, mild cardiomegaly	Yes	No	yes
Dilatation of ascending aorta	Yes	No	Unknown
Headache	14r	12yr	As long as she can remember
Anxiety attacks	No	12yr	As long as she can remember
Palpitations	14yr	No	As long as she can remember
Pertinent family history	No	No	Not Yet

UH isn't alone in dropping the ball with Lori's case, there are too many doctors to list. What I can say is that the current state of the medical profession, from costs to care provided, is definitely in need of an overhaul. When patents get processed through a doctors office like burgers through a fast food joint there is definitely something wrong with the system. I can honestly say at this point I don't know how to fix it. As for the Obamacare Law I think it sort of compares to the current state of Major League Baseball. There is no balance between the teams and MLB's version of revenue sharing” definitely is not working. Until MLB owners and players agree on a hard salary cap with revenue sharing like the NFL, baseball will remain broken. So it is with the government and health care. Until they can agree, the general public loses like the fans do in baseball, a substandard product at ourageous prices. Make no mistake, I am not advocating more government involvement in healthcare. Take Lori's case for example, she has 3 small hernias along her incisions from the most recent abdominal surgery. Included with that is a diagnosis of complex regional pain syndrome from all the nerve damage done to her abdomen over the years. One of the surgeons who did the cutting said he would not fix the hernias until Lori had her pain under control. The pain management doctor indicated she needs a pain pump surgically inserted near her spine to inject morphine into the nerves affected. A pain pump however, would prohibit Lori from getting scanned for the tumors. In addition,the small mesh used to fix hernias would only get in the way in the event Lori needs to be opened up in the future to remove the tumors. The end result is Lori has to to deal with all of it while I try and pick up the pieces, put on a happy face and pretend like nothing bothers me when I pick up the phone at work to do my job. As I am one of the thousands of customer/technical service persons you may interact with on the phone in the near future, try and remember a “normal hectic” day for you, simply may not compare to the next person you speak with on the phone, even if you have had to wait an extended period of time. Since everyone wants what you want, the “latest and greatest consumer gadget,” demand will most certainly exceed suppy as it almost always does. Most of you will have to wait, and there will be nothing the persons on the other end of the phone will be able to do about it. Ok, now that I've begun to ramble about my job, its time to wrap this up. I need my sleep. Until next time, or as Joe Tait used to say “Have a good night everybody”

NIH visit two

Here's the update from our second visit to NIH.

Lori was scanned via CT and PET with contrast while at NIH. This last trip differs from the first in he number of scans and the different agents used to highlight the tumors. Put simply, since NIH now has a baseline for tumor size and location it is much easier to track without having to put Lori through the full battery of CT / PET/ MRI scans with 3 different contrasts/ radioactive elements unless something significant changes are noticed on the first run of scans. In other words, if the tumors haven't gotten a lot larger or spread to new locations, there is no need for additional testing. After getting to NIH on Saturday, Lori had a blood draw Sunday morning and the 24 hr jug to test for catecholamine levels. Monday was a full body CT with contrast followed later in the day with a PET scan. Tuesdays are always clinic day. That is where patients meet with the individual research fellow that follows their progress. After that we met with the head of the research protocol Dr. Pacek. He gave us what I consider to be extremely good news all things considered. Only two of the six tumors have marginally grown in size. The others appear to be the same size as the April scans. There also appears to be no new tumors in any other locations. I was absolutely ecstatic at hearing this. Dr Pacek indicated the tumors showed to be stable, which he also confirmed as good news in this situation. During the first visit to NIH, in addition to the genetic testing of Loris tumor samples, they also tested for genetic mutations of the succinate dehydrogenase complex. There are 4 subunits within this complex and a mutation on any of the 4 can increase the chances of developing a pheo/ para or other types of tumors depending on the specific mutation. Some of these mutations can be passed down from generation to generation, so once a pheo/ para is discovered, genetic testing is the best way to determine of direct relatives also need to be tested based on the mutation that may be found. The four subunits where mutations have been found are known as SDHA, SDHB, SDHC, and SDHD. Lori was tested for the last 3 listed and was negative for all three. That means she did not have any of the most commonly found mutations known to happen within pheos/ paras. These three subunits are also known as tumor suppressing genes where as The results of the testing for the new genetic mutation known to cause the secondary polycythemia type symptoms listed in earlier posts was also negative. Dr. Pacek indicated he was unsure if the negative test was due to the quality of the the tumor tissue sent to NIH from University Hospitals or not. He did indicate they have different procedures for preserving tumor tissue samples than other hospitals due to the research mandate. Since our first visit in April, Dr pacek indicated he had confirmed two more people with the unnamed genetic mutation and wanted to retest Lori's DNA and tumor DNA. The age at which Lori began showing symptoms of the elevated red blood cell counts and started her entire medical journey, was still in line with the other four people already confirmed to have this new mutation. This mutation can be inherited. Dr Pacek indicated there will be more information available when he publishes a paper on it in an upcoming New England Journal of Medicine. Like I said before I am overjoyed by the news that the tumors have not spread or show signs of being aggressive. The results of the genetic testing most likely will not be known for some time. We should be going back to NIH toward the end of October or early November depending on the NIH schedule.

That's all for now....

Lori's history part three

When I left off from the previous post Lori had made it out of ICU and moved up to her room. We had been told she would be able to return to work 8-12 weeks after the October surgery for possible light duty at the world’s largest retailer. Lori’s stay in the hospital after tumor removal was for the most part uneventful other than a few nights of being hypotensive and the shallow breathing that would be expected with a major abdominal surgery and a patient that smokes. For most of those days when I was keeping watch in her room I was also researching pheos/paras. I was concerned about the pathology from the July surgery that came back from the lymph node that had been removed. Metastatic cancer regardless of the type or organ will get any ones attention. While not known as a particularly aggressive cancer, I couldn’t help but wonder if it wasn’t known as an aggressive type simply because it is so rare to begin with. Lori came home without much incident. Compared to her first surgery it seemed there was much less in the way of complications. She was discharged with the standard set of instructions. Take it easy, rest, no heavy lifting, watch your BP, if an emergency arises, go to the ER. We did all of that. During one of the follow up appointments with one of the surgeons Lori indicated she still had a lot of pain on her left side by the incision. She said it hurt more at that end of the incision than the other end by her belly button and wondered why since everything seemed to be healing up ok. It was then that we were told they (the surgical team) had to break 4 of her ribs to get at the paraganglioma in the lymph node behind her heart and it may take up to year for her ribs to heal and be pain free. It was also when we learned that the aforementioned para was indeed metastatic. When Lori asked what could be done about the pain she was referred to a pain specialist. This specialist to me is no different than a drug dealer with a license. Simply put he tried every narcotic you could think of in various doses to control Loris pain. All they did was turn Lori into a zombie. The pain she was feeling did not go away. She describes it as a constant burning on her skin. The deep pain she had been feeling as a result of the broken ribs has subsided over the course of the last yr but the burning on the skin has not. It was at these “follow-ups” that we began searching for better answers to all of our questions. Most of the time when we would see a doctor such as the oncologist for the tumors itself; he would refer us back to one of the surgeons for the pain/ mild swelling. The surgeons in turn would refer us to the pain management guy. (I refuse to call this guy a doctor at this point, unless it’s Dr Bullshit) Lori did have an MIBG test in January 2012 that came back negative as well as a CT scan. The CT scan did indicate several lesions on 2 lobes of her liver. There were three lesions in total. The oncologist had his own theory on how Lori developed the cancer in multiple spots of her body all of a sudden but nowhere in his theory did he mention genetic mutation. We asked about possibly redoing the MIBG test. He said no need to rescan, since there was no indication of any more tumors. I mentioned that approximately 60% of those tested with MIBG scan failed to show a tumor even though they may be present. He ignored my question; it was like I hadn’t even spoken. Lori asked about the lesions in the liver he replied, don’t worry about those, everyone has lesions of some sort in the liver. Lori asked if he had to pick a cancer stage associated with other cancers what would it be? He replied stage 4. Lori asked if it was safe to return to work he said yes as soon as she could withstand the pain she had been having. Lori asked about having a better quality of life before the tumors were removed, he replied “This is as good as it’s going to get for you, might as well accept t and move on. You probably won’t be able to have the same life as before.” With that he handed us a pamphlet for a cancer support group, shook our hands and said he would set up a follow up CT in 6 mos. We have not been back to see him either. We got an appointment confirmation call for the CT scan (we had forgotten about it) on the way down here for our second visit to NIH. I think it was set for next week. Needless to say we canceled it. Lori still gets the burning pain on her skin due to what has been termed regional complex pain syndrome. As one of the surgeons explained, it is due to the damaged nerve endings in her skin from the multiple abdominal procedures. There really is no fix since nerves probably will not regenerate. Since her first abdominal surgery in 1978 she had decreased feeling in a large part of her abdomen but never any pain. The Dr Bullshit guy wants Lori to have a permanent pain pump inserted so she can deliver morphine in small doses right to the affected area. Since the pain pump is metal it would mean she could not be properly scanned in a CT or MRI machine if she ever needed to in the future. Through all of this, the one constant has been Lori’s endocrinologist. She has ordered the right blood tests and they had continued to indicate that Lori still had a pheo/para somewhere. She has also kept Loris BP under control without using dibenzaline, since Lori did not like the way it made her feel prior to the surgeries, or the cost of it.

It was the end of January into February that we discovered the resources listed on the pheoparatrooper.org website as well as the support groups on facebook. Lori began emailing different people here at NIH and by the time she had rounded up as many records as she could from over the previous thirty years, we learned we were accepted in to the protocol for research and testing. We first came to NIH the first week of April 2012. Dr Pacek was extremely interested in Loris condition with the tumors and how they have been affecting her blood since the age of 6-7. Most pheos do not cause red blood cell counts to rise. Red blood cells are produced in your bone marrow and depending on geographical location and race, are generally the same for everybody. Anything that causes a prolonged low oxygen state can induce increased red blood cell count in a normal person. Think of the decendants of the Incas or someone that spends their entire time in the mountains where the air is thin with less oxygen. Over time you body develops a physiological response and increases red cells in attempt to deliver more oxygen to the brain. Other things such as smoking will cause secondary polycythemia. As I have posted in part one of Lori’s history, she did not start smoking at the age of 6. Lori’s skin gets really pink (think the shade of Miss Piggy) when her RBC is elevated. The highest we have seen on her lab work is a hematocrit level of 64. The following is from Wikipedia.

The hematocrit (Ht or HCT) or packed cell volume (PCV) or erythrocyte volume fraction (EVF) is the volume percentage (%) of red blood cells in blood. It is normally about 45% for men and 40% for women.[1] It is considered an integral part of a person's complete blood count results, along with hemoglobin concentration, white blood cell count, and platelet count.

After meeting with the hematologists here at NIH, they indicated Loris lab work showed consistent higher than normal levels of erythropoietin in her blood. What is that and how does it figure into Lori’s elevated blood? The following is also from Wikipedia.

Erythropoietin, or its alternatives erythropoetin or erthropoyetin (/ɨˌrɪθrɵˈpɔɪ.ɨtɨn/, /ɨˌrɪθrɵˈpɔɪtən/, or /ɨˌriːθrɵ-/) or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine (protein signaling molecule) for erythrocyte (red blood cell) precursors in the bone marrow.

Lori and I then asked, "Does this mean we can say for sure the pheos/ paras are causing her blood condition of secondary polycythemia?" Until April 2012 every hematologist refused to commit to an answer to that question. The short answer was yes. Dr Pacek indicated he had discovered two other women, one from Croatia one from the US, that had the same symptoms, were of similar age. They both had a brand new genetic mutation, so new it as of then did not have a name. That was the good news as far as we were concerned. It validated all those battles with hematologists that kept insisting Lori’s condition was self inflicted due to smoking. The other news was that yes Lori did have six active pheos/paras, 3 in her liver, one on her right adrenal, one in front of her L1-L2 junction and one in her pelvis. Since this was the first round of various scans done at NIH, we were not given definite treatment plans since we did not know how aggressive these tumors would be. That would require a follow-up visit. In the three months since that visit we have continued to follow up with the endo that cares. She admits she has not had a metastatic pheo patient before but she is willing to work with NIH and try anything and do anything it takes to keep Lori alive with a decent quality of life. That’s all I can ask for. We have also begun searching out possible treatment paths to reduce the tumor burden if Dr Pacek indicates its needed. That Dr. is located at the Cleveland Clinic and he has indicated a willingness to work with whatever NIH recommends.

This post and the two before it is a condensed version of the last year of my life leading up to our second visit here at NIH. The results of this visit will be in a post after I get home at the end of the week..