It has been almost two years since my 45-year-old sister was originally
misdiagnosed as having ovarian cancer, which turned out to be Pseudomyxoma
Peritonei (PMP), more specifically, Disseminated Peritoneal Adenomucinosis –
origin: appendix (DPMA). In those two years, I have had the opportunity to study
and visit the major U.S. hospitals and doctors that deal with this disease. I have
talked to surgeons, oncologists and patients. I’ve have done my homework,
knowing that my sister’s life depended on it. I would like to share this information
with you in the hope that it may assist you or your loved one in fighting this
disease. So, forgive me for the length of the posting, but I want to be sure that I
include all relevant details.
The disease comes in two general types: Adenocarcinoma and Adenomucinosis.
Of the two, adenomucionosis appears to be somewhat more benign as it is not
technically a cancer and thus will not usually spread to interior organs. Few
doctors, however, differentiate between the two. Even at MD Anderson Cancer
Center, it is all called “adenocarcinoma.” Dr. Sugarbaker, however, prefers
limiting the definition of PMP to adenomucionosis only and excludes cases of
peritoneal carcinomatosis from this definition. A good article on this can be found
at: http://www.surgicaloncology.com/pmp.htm.
This is a rare disease…perhaps fewer than 1,000 cases are known to currently
exist. Accordingly, you need a real specialist. Traditional cancer surgeons don’t
know enough about the disease to treat it correctly. Even a top oncology surgeon
at Memorial Sloan Kettering Cancer Center can misdiagnose it, as it happened
with my sister. Having a knowledgeable specialist do the first surgery is perhaps
the most important factor in the treatment of this disease, as surgical scaring
makes every surgery thereafter more and more difficult.
Most women tend to be in their late 30’s to early 40’s when first diagnosed. I
don’t know the average age for men… but have encountered patients from early
20’s to late 70’s. The most common initial symptom is increasing abdominal girth.
Men can also show inguinal hernias and women can show ovarian masses.
In the case of my sister, it was an ovarian mass that led to her eventual
diagnosis. Perhaps 4 or 5 years ago, her appendix developed a mucinous tumor.
Unnoticed, the appendix eventually burst and spilled out all the mucinous stuff
throughout her abdominal cavity (the peritoneum). When her ovary ovulated (i.e.
“opened”), some of the mucinous stuff got inside and started growing within the
ovary. By the time the doctor noticed the ovarian mass approximately two to
three years later, it was already 9” in diameter. Which brings me to her initial
misdiagnosis. After reviewing a CT scan, an oncologist at Baptist Hospital in
Miami, Florida diagnosed it as Ovarian Cancer. I had the Chief of the Gynecology
Service at Memorial Sloan Kettering Cancer Center review her case. He agreed
with the original diagnosis.
Within a few days, we had already scheduled my sister for surgery at Memorial
Sloan Kettering. During surgery, the surgeon found such copious amounts of
mucinous stuff disseminated throughout her abdominal cavity that he limited the
surgery to removal of her ovaries. He thought that, “no further benefit could be
afforded to the patient” (i.e. let’s close her up, it is a lost cause). In hindsight, a
mistake, but not an uncommon first experience for patients diagnosed with this
disease. Which goes to show you that even one of the best oncology surgeons –
the Chief of the Department – at one of the best cancer institutions in the world –
Memorial Sloan Kettering – can misdiagnose the disease and might not even be
able to recognize it under the scalpel. This is the nature of a rare disease. And
this is the reason why you need a specialist. In my sister’s case, it was not until
seven days after the surgery that the pathology of the tumor revealed the true
diagnosis – Disseminated Peritoneal Adenomucinosis – origin: appendix. Here is
where my research on the treatment options for PMP commenced.
At Memorial Sloan Kettering, post pathology, the doctors recommended periodic
cytoreduction (i.e. debulking). Their approach would be limited to debulking of the
tumor through surgery every few years… no chemo, nothing else. But not finding
a true specialist on this disease at Memorial Sloan, we decided to look
elsewhere. Just for the record, however, I have nothing against this hospital and
its doctors. On the contrary, it is a great cancer research center… and should be
on the short list of most cancer patients. The only “challenge” we encountered
with Memorial Sloan was on insurance issues. If they don’t accept your
insurance, be prepared to have to pre-pay for surgery. In any event, we did not
see Memorial Sloan at the vanguard of this disease.
Anyone afflicted with PMP would be wise to study all the literature and research
of Dr. Paul H. Sugarbaker of Sugarbaker Oncology Associates at The
Washington Hospital Center (http://www.surgicaloncology.com). Certainly, Dr.
Sugarbaker is one of the most experienced surgeons on this disease. Most often,
Dr. Sugarbaker will only take your case if he believes he has a shot at curing
you. He will rate the severity of the case from I to IV (not to be confused with the
four stages of cancer). In the case of my sister, she was rated a IV+, which
meant he would have to remove, along with a bunch of other organs, her entire
stomach and colon. This would have left her with a permanent bag instead of her
colon (a permanent colostomy). Even though Dr. Sugarbaker graciously agreed
to take her case, we were not prepared for such a radical intervention at that
time. Had she been at an earlier stage of the disease, however, Dr. Sugarbaker
would have been a very real option for us. He has permanently cured many
patients. Others, however, have also died in the process of “going for the
permanent cure”.
Among the PMP surgeons, Dr. Sugarbaker is probably the most aggressive and
therefore the most controversial. At an early stage of the disease, Dr. Sugarbaker
can probably cure it without having to leave you with a permanent colostomy
bag. At more advance stages of the disease, surgery for a permanent cure
becomes more complicated. A good thing about Dr. Sugarbaker is that he will tell
it to you as he sees it. If surgery with Sugarbaker becomes your choice, you’ll
have to get into optimal physical shape; as he will tell you, “your survival could
depend on it.” One more thing... a few former patients complained about the
attentiveness of the hospital staff and suggested that a family member should be
with the patient at the hospital at all times. If your disease or health is past the
point where Dr. Sugarbaker believes he has a shot at curing it, he will most likely
refer you to a Dr. Sardi.
Before I tell you about other surgeons and hospitals , I need to tell you about
IPHC, which stands for Intraperitoneal Hyperthermic Chemotherapy. Not all PMP
surgeons use it – that’s why you need to know about it. To explain IPHC, I’ll
quote Dr. Brian Loggie. “A major difficulty in treating patients with cancer that has
seeded widely on lining surfaces in the stomach cavity (abdomen, peritoneal
cavity) is that it is often not possible to remove all the cancer cells.” IPHC is used
as “an effort to ‘sterilize’ any remaining tumor cells” after radical surgical tumor
removal. “The term ‘intraperitoneal’ means that the treatment is delivered to the
stomach cavity. The term ‘hyperthermic chemotherapy’ means that heated fluid
(hyperthermic refers to temperatures greater than normal body temperature) is
circulated (perfused) throughout the stomach cavity (abdomen).” The heated fluid
contains an anti-cancer drug called Mitomycin-C.
So in plain English… the goal is for the surgeon to try to take out as much tumor
as possible… and then circulate this heated fluid for a couple of hours around
your abdomen (while your abdomen is still open) to kill the rest of the cancer
cells. The issue here is that the surgeon will really not know for sure whether or
not you are a good candidate for IPHC until the time of surgery. The doctor has
to evaluate the plusses and minuses of using it after surgery based on your
individual case. As with all treatments, it has risks. If you go to any of the
surgeons that use IPHC (which include Brian Loggie from Creighton University,
Paul Mansfield from MD Anderson, and Paul Sugarbaker from Washington
Hospital), you will receive complete documentation on this treatment.
Now, back to the doctors. At Mayo Clinic in Rochester, Minnesota, there is a
wonderful surgeon named John Donahue. My sister loved him. As of 2002, he
had performed the cytoreductive surgery on 60 + patients over a 15 year span.
He is very knowledgeable and caring. My sister felt very comforted in learning
that the surgery was not a one shot deal… that more surgeries could be done in
the future if he couldn’t remove all the stuff. We were not as impressed with the
Oncology team nor with the proposed oncology treatment, however. They
suggested an intraperitoneal chemotherapy treatment beginning five days after
surgery. We felt that giving the intraperitoneal chemotherapy five days after the
operation would not be as efficacious as IPHC due to the tissue scarring that
occurs immediately after the operation (scarring prevents the chemo from getting
into the tissue). They also proposed some radiation, which can make it a little
more difficult to perform more surgeries in the future. PMP patients that have
been operated at Mayo feel that this is a great hospital, with phenomenal patient
care, totally focused on the patient and not the economics of the business. We
loved the doctor… but felt that we wanted a little more aggressive treatment.
That left Dr. Loggie and Dr. Mansfield. Loggie was not taking new patients at the
time because he was in the process of transferring to Creighton University to set
up the clinic there. So, on we went to visit Dr. Mansfield.
Dr. Paul Mansfield from MD Anderson Cancer Center in Houston, Texas
performs a procedure similar to that of Dr. Sugarbaker, but because he is not
infatuated with “going for the cure” he tends to place more emphasis on the
patient’s quality of life post surgery. As of 2002, he had performed 100+
surgeries and only 3 patients had died from complications of the operation itself.
He told us about each of those 3 patients (which appeared to be isolated
incidents) and he related what he learned from each case. He did not think that
he could “cure” my sister by getting all the stuff out… but he said he would
certainly try his best. He estimated that the operation would take approximately
10-12 hours with an additional 2 at the end for the IPHC.
We scheduled surgery for August 6, 2002 with Dr. Mansfield. We got there about
a week prior to the operation itself for a battery of tests, CT scans, and lab work.
All done with great caring and professionalism. But, despite Dr. Mansfield’s
wonderful attention to our case, walking the long hallways from one department
to the next and the environment in general made my sister feel as if she was
inside a cancer treatment factory, as one more patient going through the
“assembly” line. We were comforted, nevertheless, knowing that we were at one
of the best cancer centers in the world and under the supervision of a true PMP
surgeon specialist.
Things did not go well during surgery. Not because of the doctor or the hospital,
but because of my sister’s particular type of tumor. As Dr. Mansfield puts it, “the
tumors come in all sorts of different types.” And my sister’s tumor was so
encrusted into the organs that too much damage would have been done trying to
remove it. He considered removing the entire stomach and colon (as Dr.
Sugarbaker told us he would have to do), but opted for not doing so because he
would have still left disease in the deep pelvis and up behind the liver. He also
opted for not doing the IPHC because, given the abundant amount of tumor still
left, he thought it would be better treated with systemic chemotherapy (and doing
the IPHC would have delayed the start of the systemic chemo). He did tack the
stomach closer to the surface to make things easier at later stages of the
disease.
Not much has been posted on the later stages of the disease, so if you don’t
want to read about it, skip this paragraph and go on to the next one. The reason
why this is a deadly disease is not necessarily because it invades the organs…
but instead is because it suffocates the organs, preventing them from moving.
The entire intestinal tract, in particular, gets stiff, which prevents the food from
being digested and excreted correctly. Like a clogged drain, things end up
backing-up. This is the reason why he tacked the stomach closer to the surface,
so that in later stages of the disease, a port could be more easily installed directly
into the stomach and used as “clean-out”.
By now you must be thinking… boy, there is no hope for this woman’s case. But
au contraire, we firmly believe that nothing is impossible, particularly with
unquestionable Trust in God. More on this later, but I suggest you don’t try to
fight this disease alone – God is a wonderful partner.
Before I tell you about her systemic chemotherapy treatment, you need to know
about “establishing a base line” through CT scans and tumor markers. To assess
whether a particular treatment is working or not, the tumor needs to be compared
to its status prior to treatment. This is done through CT scans and through tumor
markers. The tumor markers measure the level of particular proteins excreted by
the tumor… the more protein that is excreted, the higher the level of the marker
and the higher the probability that the tumor is growing. The markers most used
for this disease are CEA, CA19-9 and, for women, CA-125. You can do some
research on the specifics of each, but what is important is to see the trend in their
numeric values over time. It is difficult to judge the numbers from one month to
the next, as the values can fluctuate by quite a bit; therefore, it is best to look at
the trend. You should also be careful in comparing the numbers from different
laboratories… it is best, to be consistent in the laboratory doing the test. Finally,
you should also know that the normal ranges can vary depending on the test
method. For CEA, as an example, one test will have the normal range from 0 to
2.5 for non-smokers and from 0 to 5 for smokers, while another test method will
have the normal range from 0 to 5 for non-smokers and 0 to 10 for smokers. So,
be sure to compare apples to apples.
We started with systemic chemotherapy on mid-November 2002 (about 3 months
after the operation). Through an IV, she received 300mg of Ivunotecam and
250mg of Oxiloplatinum during approximately a 6-hour period. 21 days later, the
procedure was repeated. She was uncomfortable for the first couple of days after
each chemotherapy treatment… with headaches, nausea, and vomiting. The
second cycle was actually tougher than the first. Her hair thinned out, but she
never lost it all. The CT Scans and tumor markers did not show an improvement,
and therefore Dr. Wolff, the oncologist at MD Anderson Cancer Center, switched
her chemo treatment to140mg of Platinol through an IV followed by 3500 mg of
Xeloda per day for 14 days. 800 mg per day of Celebrex was also added to her
regimen. This was repeated every 21 days (i.e. the Platinol given once, Xeloda
for 14 days on, 7 days off, and Celebrex uninterrupted). She did three cycles of
this routine. Platinol had the similar side effects of headaches, nausea, and
vomiting for a couple of days. The Xeloda she tolerated quite well. Celebrex is an
anti-inflammatory, which Dr. Wolff started using based on some research done
by Dr. Loggie (they all know each other). Again, no improvement was detected
either through the CT scans or tumor markers. By now, Dr. Wolff had given up
and suspended all further treatment. This was around March of 2003.
The most prudent course of action would been to contact Dr. Loggie at this time,
but having heard some encouraging results from a few PMP patients taking
Thalidomide, we wanted to give it a try for a few months. Thalidomide is the
same medicine that was used by pregnant women in the late 1950’s and early
1960’s to combat the symptoms associated with morning sickness.
Unfortunately, when taken during the first trimester, the medicine prevented the
proper growth of the fetus and resulted in severe malformations of the babies.
Thousands of Thalidomide babies were born around the world with missing limbs
and other horrific deformities. The drug was pulled off the market, but some
years later a group of scientists sought other uses for the drug that had created
such atrocious, birth defects. The theory was that because the drug created the
malformations by preventing blood from flowing into rapidly growing tissues (as
those in a fetus), it could also be used to atrophy the growth of cancer (also a
rapidly growing tissue). The drug has now received FDA approval for the
treatment of leprosy and is also in various stages of clinical trials for various
forms of cancer.
A few years ago, a Doctor, now diseased, recommended this drug to a woman in
California afflicted with PMP. She started taking it and after a few months saw
her tumor shrink to undetectable levels. This woman also told me that the tumor
started growing again after she stopped taking the drug but that it shrank again
after she resumed the regimen. After consulting with her current doctor, a
gynecologist-oncologist at Stanford University Medical Center, and evaluating the
possible side effects, we decided to give Thalidomide a try. This was in addition
to the 800mg per day of Celebrex, which we never discontinued because we
knew it was part of Dr. Loggie’s standard regimen (more on this later).
Thalidomide is not inexpensive, in the US the regimen would cost a few thousand
dollars a month, which may or may not be covered by insurance. But since my
sister lives outside the US, we were able to obtain it directly from Penn
Pharmaceutical in England at a fraction of the US cost. We started at 200 mg per
day (at night) about eight months ago, increasing the dose by 50mg every couple
of weeks until she reached 400 mg per day. She tolerated the drug reasonably
well. Side effects can include severe constipation (which needs to be
aggressively controlled though diet and stool softeners or it can send you to the
hospital), peripheral neuropathy (numbness on body extremities such as fingers
and toes), sleepiness (hence why it is taken at night), and general fuzziness with
some memory loss.
At the beginning, her tumor markers showed such a significant improvement that
even Dr. Wolff was encouraged by the results and recommended that we
continue with it. The good news, however, did not last long. While the CA-125
tumor marker continued to decline, the CEA level reversed its downtrend and
started rising once again after five to six months of having commenced with
Thalidomide. At about the same time that her CEA level began to increase,
coincidentally or not, her abdomen began to swell and in a matter of eight to ten
weeks had already reached the size of a six to seven month pregnancy.
Fortunately, a CT Scan revealed that the “abdomen growth” was mostly liquid
(know as “ascites”), and we therefore scheduled her for a Paracentesis. This
relatively simple procedure is used to aspirate the liquid through a fine needle or
catheter inserted in the abdomen. Using local anesthesia only, a radiologist
generally performs the procedure using an ultrasound to guide the correct
placement of the needle. Because the tumor in PMP patients tends to “trap” the
fluid in non-connected pockets, it is important that the radiologist be aware of this
(otherwise he may not extract all the fluid). In my sister’s case, they extracted 6.2
liters (about one and one-half gallons) of a yellowish/green, free-flowing fluid
through two aspirations.
One of the benefits of the IPHC that my sister did not have done is that it
generally prevents the ascites from recurring. Some doctors will also treat the
ascites through a non-heated, intraperitoneal chemotherapy. At MD Anderson,
they have recommended that we wait until she needs to be ”tapped” again to
perform this procedure. In a “reverse paracentesis” format, they would simply
inject a chemo drug, known as Taxol, directly into her abdominal cavity.
Clearly, it was now time to visit Dr. Brian Loggie at Creighton University Medical
Center in Omaha Nebraska. I sent to his assistant, Dan Dollison (CUMC Cancer
Center, 601 North 30th Street, Suite 2321, Omaha, Nebraska, 68131), a
complete chronological medical history (everything from a description of her first
symptoms, to the official records of all operations, pathology reports, tumor
marker levels, and CT Scans). I also arranged for non-stained, tumor slides and
tumor blocks to be sent to Dr. Loggie’s office directly from MD Anderson and
Memorial Sloan. I believe that helping the doctor treat the patient is part of the
patient’s responsibility. And to this end, providing all the medical records well
organized and in chronological order is the perfect way of helping the doctor. A
detailed cover letter along with a binder containing all the relevant information will
go a long way in getting a quick response from a doctor.
Dan Dollison gave us an appointment to visit with Dr. Loggie on December 22,
2003, just a few weeks after receiving all my information. Creighton University
Medical Center is located a few miles from Omaha’s airport and an even shorter
ride from downtown Omaha. A fairly prosperous town, we liked it from the
moment we got there. And unlike the cavernous hallways of most cancer centers,
the Creighton medical center is a relatively small facility. To us, being Catholic,
having the statue of St. Joseph greet us at the entrance of the hospital was very
comforting.
Meeting Dr. Loggie was a wonderful Christmas present. After a physical
examination of my sister and a thorough discussion of her medical history, he
reviewed all her CT Scans with us (7 in all). In this process he showed us the
progress of the disease. More accurately, I should say the lack of progress of the
disease, as since her operation at MD Anderson approximately a year and a half
ago, the tumor has stayed basically the same. It has shrunk a little around the
liver and has grown a little around the pelvis, but for all intents and purposes, it is
about even.
What I believe sets Dr. Loggie apart from his colleagues in the treatment of this
disease is that he will approach it from both a surgical and a tumor biology
perspective. He will perform surgery when necessary, but as he says, “treating
this disease surgically is like hunting with a limited number of arrows; you want to
be certain that you use an arrow when you are sure to hit the target.” He will
study the biology of each patient’s tumor and treat it accordingly. In my sister’s
case, he sees her PMP as a chronic disease (i.e. a long term disease) that needs
to be treated with a long-term perspective. To this end, she needs to be treated
with medicines that can be well tolerated over many years (i.e. not a one shot
chemo treatment), and then surgically as necessary.
He attributes the tumor’s lack of growth and her general well being (she feels
perfectly healthy) to Celebrex, and was pleased to see that we never discontinue
using it. This medicine, being an anti-inflammatory, also prevents inflammation of
the organs that have been surrounded by the tumor. While many years ago he
also prescribed Thalidomide, he believes that he has better alternatives now and
asked her to discontinue using it. He says that, eventually, the Thalidomide side
effects catch up with the patient. We were also beginning to see this ourselves –
as her memory lapses, while a reversible condition, were increasing in frequency.
He is still in the process of studying her tumor, but discussed a number of
available treatment options including adding Xeloda to her daily Celebrex
regimen. We are now on a schedule to meet with Dr. Loggie every three months
and feel that we are in great hands.
A few closing remarks. Before visiting Dr. Loggie, we also went back to MD
Anderson and, at the recommendation of Dr. Mansfield, met with Dr. John J.
Kavanagh, the Chair of the Department of Gynecologic Medical Oncology. He
had my sister’s tumor tested for EGF Receptors to see if her tumor could be
treated with Iressa. Basically, the cells in certain tumors have these receptors
that permit this medicine to get inside the cell, and once there, the medicine can
destroy the cells from within. Fortunately, my sister’s tumor tested highly positive
for the presence of these receptors, and he has therefore recommended that she
start on a regimen of 500 mg of Iressa on a daily basis. Since Dr. Loggie is also
testing her tumor for this, we will await Dr. Loggie’s recommendation.
All of the doctors we have visited are highly competent and are the specialists for
this rare disease. You are probably in good hands if you are with any of them.
We are grateful to all as they have all opened their doors to us and have all been
willing to help us. At this stage of her disease, we personally feel most
comfortable with Dr. Loggie’s treatment options, and he is now our primary
doctor.
Clearly, my sister’s disease is still a very serious condition, but nevertheless we
believe that it is possible to cure it. How it will happen I do not necessarily know,
but, as we pray, we know that our prayers are not meeting deaf ears. We have
already seen many of our prayers answered; it’s been almost two years since her
original diagnosis, her tumor has not spread further, and she is enjoying life as
any other healthy person would – perhaps even more. Yes, we have had our
challenges, but in the continuum of an infinite life, a few years of challenges are
but a second; a second nevertheless that can help us develop a closer
relationship with God, our creator. Believe in His Word, and, if you don’t doubt,
His Word will become reality within you.
I hope this information helps you; if there is anything I can do for you, please
contact me at jas_rand@yahoo.com.
Jose