Re: New: intro, questions, greetings

[Guest guest]

> I'll try to respond to some of your questions

Wow, not so easy to keep up with this board. Thanks, , for

taking the time to respond. I know I can be inquisitive, sorry.

> Diagnosis time was terrible; the doctors were very blunt ... it

didn't take him long to realize that the prognosis is poor. I think

it weighs heavily on him, but he takes his medications and

supplements faithfully, and avoids alcohol, and eats well, and this

has resulted in his blood work becoming near normal (he still has

slightly elevated alkaline phosphatase!) over the last 3.5 years.

The appearance of his colon has improved significantly since his

initial colonoscopy when UC was first diagnosed 3.5 years ago. He has

seen and these improvements himself, and this makes taking all the

medications seem worthwhile to him. I think that he realizes that

he has to live and enjoy his life now! He's done well at college,

and is now applying to medical school.

He sounds like a motivated young man; you must be incredibly proud of

him. I'm not sure what it will be like when our son knows and

comprehends every detail, but I wanted to know what it's been like

for others. Thank you for sharing. And, I wish your son well in

medical school.

>It seems to me that if intestinal inflammation is allowed to persist

for a long time, this could promote cancer. So, calming the UC down

with asacol (5-aminosalicylic acid) and using ursodiol to reduce

liver injury, and compete against toxic bile acids being delivered to

the intestines, might make a difference in the long-run in terms of

occurrence of colon cancer and bile-duct cancer. Both 5-

aminosalicylic acid and ursodiol have been shown to reduce colon

cancer, and preliminary results suggest that ursodiol may also reduce

the incidence of cholangiocarcinoma. I think that in addition to

keeping inflammation in check, it is important to prevent vitamin

deficiencies from developing.... is Wyatt's genetic condition

familial adenomatous polyposis

Our son's dr thinks that coating the bad intestinal bacteria with

good may 'quiet' the PSC (at this early stage); he feels the PSC is

an immune response to the bacteria of UC in our son, so he's using

only the probiotic right now. He doesn't know how long it may 'quiet'

it for or if our son will respond in that way to only the probiotic,

but he's using the first month or two post-dx to try it out (before

moving on to vancomycin). He hasn't mentioned urso at all yet, but

my husband and I are going in with a list of questions when we see

him this month; some we'd rather ask without our son present.

As for the cancers, I'm really concerned about those for our son.

FAP is the genetic condition he and my husband have (not my husband's

parents or brother, though --the gene mutated within my husband to

begin in our family; we learned of FAP when my husband got cancer).

Wyatt is lacking a tumor suppressor on the APC gene (on chromosome

5). Only the organs/systems regulated by that gene are a concern,

but the liver, stomach, esophagus, duodenum, and colon are some of

those (the brain, too, but thankfully that is not a PSC thing -so

no 'double hit'). Wyatt has been growing adenomas in his colon since

he was 7, but only a few at a time so far. He just started growing

the stomach and duodenal ones, and his liver is clear for now.

FAP 'guarantees' colon cancer, but the other cancers connected to it

just make you 'predisposed' or at higher risk. What concerns us is

putting PSC in that mix. It ups the odds in a negative way --and

we've read up on some cross-over risks from one to the other that

could spell disaster. One 'cross-over' risk is the non-cancerous

desmoid tumors on or under the skin that FAP people can get. The

under the skin ones can grow to 'impair' internal organs, some can be

impossible to remove. They tend to grow due to scar tissue, so it's

only when surgery or surgeries are performed that it can be an

issue. Before PSC, we believed Wyatt's only surgery would be the

future surgery to remove his colon when it becomes amassed with

adenomas (or they turn cancerous). With PSC, we're afraid of a whole

future of possible surgeries that could then cause a problem with

desmoid tumors. And, the 'double' liver cancer risk worries us, of

course. He's missing the tumor suppressor for the liver --how is that

suppose to help when you also have PSC? It's just endless how our

minds race putting the conditions together in a negative mix. It

really frightens us where FAP on its own was something we had

somewhat accustomed to. PSC as well feels like 'end-game' in some

ways. We could just be torturing ourselves and it may turn out that

the FAP & PSC don't harm one another as this plays out in Wyatt, but

we're having trouble holding onto that notion over the fear that they

will.

> If so, I can certainly appreciate how overwhlemed you must feel.

The only consolation must be that you are already familiar with

annual colonoscopies! Some consolation!!

How did you know about FAP? I hope it doesn't run in your family as

well and I'm very sorry if it does.

And, yes, Wyatt has had regular colonoscopies since he was 7. He

actually looks forward to going to the hospital for them b/c that's

the only time we ever buy him a new gameboy game. He'll have regular

endoscopy from now on, too, and his dr was talking about regular

liver biopsies (as well as the labs to keep tabs on the liver enzyme

levels). " Scopes " we can do; that's our area. PSC is new ground for

us.

> As far as I know, VSL#3 contains 8 strains of bacteria:... Sorry,

but I don't know if Bifidobacterium species are vancomycin resistant

or sensitive. You'll have to talk this over with the GI to see

whether vancomycin would defeat the objective of the VSL?

Thank you, .

> Asacol is a delayed release 5-aminosalicylic acid used as an anti

inflammatory medication in ulcerative colitis. Rifampin (rifampicin)

is an antibiotic, but it is often used in cholestatic liver diseases

because it has a secondary effect of altering bile acid metabolism

and transport in the liver, and reduces itching (pruritus).

Again, thank you. Are there negative side effects to these?

> Costs of attending the PSC Partners Seeking a Cure Conference are

given at:

I'm looking into it, thanks (again --you're a very helpful guy, you

know). I read over the agenda and would really like to attend.

We're checking our finances.

> I'll write to you off-line to explain what we have done financially.

Thanks, I'll go look for it or keep an eye out for it. We want to be

prepared in every way we can be.

> I think that you are doing the right thing .... he doesn't need to

know some of the big questions right now. He'll ask you more when

he's ready.

I'd be willing to wager he'll be ready before I am... but I'll at

least be prepared to tell him all even if I'm not ready (does that

make any sense at all??)

Thank you sooo much, . I've shared everything you told me with

my husband and it's appreciated by the both of us.

--Meghan, mom to Wyatt (PSC & UC 1/07, FAP 8/01)

[Guest guest]

Hi Meghan;

> How did you know about FAP? I hope it doesn't run in your family

as well and I'm very sorry if it does.

No, FAP doesn't run in our family. But I've stumbled on it

occassionaly in my reading on PSC and UC. I'm really not sure how the

coexistence of FAP with PSC + UC would affect cancer risk ... I

honestly don't know if there has been any research on this

combination?

But I think that it might not be a bad idea to consider

ursodeoxycholic acid (urosdiol) therapy for Wyatt, because there's

growing evidence that it may protect against colon cancer in PSC + UC

(let me know if you need references on this!), AND, perhaps more

importantly, preliminary results suggest that it has a promising

beneficial effect in a mouse model of FAP, particularly when combined

with a cyclooxygenase inhibitor, sulindac:

Gastroenterology. 2004 Sep;127(3):838-44.

Ursodeoxycholate/Sulindac combination treatment effectively prevents

intestinal adenomas in a mouse model of polyposis.

y RF, Cole CE, Hawk ET, Lubet RA

University of Wisconsin Comprehensive Cancer Center, Madison,

Wisconsin, USA. rfjacoby@...

BACKGROUND & AIMS: Preclinical studies in animal models, human

epidemiological data, and clinical trials in patients with

adenomatous polyposis have consistently indicated that sulindac and

other nonsteroidal antiinflammatory drugs or cyclooxygenase

inhibitors have the greatest potential efficacy among current

candidates for colon tumor chemopreventive agents. However, at highly

effective doses they all have some risk of toxicity, and their

therapeutic profile might be improved by use at lower, more tolerable

doses, in combination with a second agent acting via other

mechanisms. METHODS: Sulindac was tested in combination with

ursodeoxycholic acid (ursodiol), a naturally occurring 7-B-epimer of

the bile component chenodeoxycholic acid, for prevention of adenomas

in the Min mouse model of adenomatous polyposis. RESULTS:

Ursodeoxycholic acid caused a dose-dependent decrease in the number

of intestinal tumors. Unlike sulindac and other nonsteroidal anti-

inflammatory drugs, which are quite beneficial in the distal

intestine but are somewhat less effective in the proximal small

intestine (especially the clinically important periampullary

duodenum), ursodeoxycholate had equal efficacy throughout the entire

intestine, both proximal and distal. Combined treatment with low-dose

sulindac was less toxic, with normal weight gain and fewer

gastrointestinal ulcerations than high-dose sulindac. Combined

treatment with sulindac and ursodeoxycholate was more effective than

either agent alone for the prevention of tumors throughout the entire

intestine. CONCLUSIONS: These experiments provide the first evidence

that ursodeoxycholic acid is effective for preventing adenomas in an

animal model. Cyclooxygenase inhibition, when combined with this

naturally occurring bile component, may become a promising approach

for colon cancer prevention. PMID: 15362039.

While 5-aminosalicylates (like Asacol) have been shown to be

protective against colon cancer in ulcerative colitis, this does NOT

seem to be the case for FAP (at least in the same mouse model):

Clin Cancer Res. 1999 Apr;5(4):855-63.

Evaluation of 5-aminosalicylic acid (5-ASA) for cancer

chemoprevention: lack of efficacy against nascent adenomatous polyps

in the Apc(Min) mouse.

Ritland SR, Leighton JA, Hirsch RE, Morrow JD, Weaver AL, Gendler SJ

Department of Biochemistry and Molecular Biology, Mayo Clinic

sdale, Arizona 85259, USA.

Recent experimental and epidemiological evidence suggests that

nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the

prevention of colorectal cancer. However, the toxicity associated

with the long-term use of most classical NSAIDs has limited their

usefulness for the purpose of cancer chemoprevention. Inflammatory

bowel disease (IBD) patients, in particular, are sensitive to the

adverse side effects of NSAIDs, and these patients also have an

increased risk for the development of intestinal cancer. 5-

Aminosalicylic acid (5-ASA) is an anti-inflammatory drug commonly

used in the treatment of IBD and may provide protection against the

development of colorectal cancer in these patients. To directly

evaluate the ability of 5-ASA to suppress intestinal tumors, we

studied several formulations of 5-ASA (free acid, sulfasalazine, and

Pentasa) at multiple oral dosage levels [500, 2400, 4800, and 9600

parts/million (ppm)] in the adenomatous polyposis coli (Apc) mouse

model of multiple intestinal neoplasia (Min). Although the ApcMin

mouse is not a model of colitis-associated neoplasia, it is,

nonetheless, a useful model for assessing the ability of anti-

inflammatory agents to prevent tumor formation in a genetically

preinitiated population of cells. We used a study design in which

drug was provided ad libitum through the diet beginning at the time

of weaning (28 days of age) until 100 days of age. We included 200

ppm of piroxicam and 160 ppm of sulindac as positive controls, and

the negative control was AIN-93G diet alone. Treatment with either

piroxicam or sulindac produced statistically significant reductions

in intestinal tumor multiplicity (95% and 83% reductions in tumor

number, respectively; P < 0.001 versus controls). By contrast, none

of the 5-ASA drug formulations or dosage levels produced consistent

dose-progressive changes in polyp number, distribution, or size,

despite high luminal and serum concentrations of 5-ASA and its

primary metabolite N-acetyl-5-ASA. Thus, 5-ASA does not seem to

possess direct chemosuppressive activity against the development of

nascent intestinal adenomas in the ApcMin mouse. However, because

intestinal tumor development in the ApcMin mouse is driven by a

germline mutation in the Apc gene rather than by chronic

inflammation, we caution that these findings do not definitively

exclude the possibility that 5-ASA may exert a chemopreventive effect

in human IBD patients. PMID: 10213222.

> Are there negative side effects to these (asacol and rifampin)?

There sure are, but fortunately our son has not experienced any of

them:

http://www.gicare.com/pated/mesalamine.htm

http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202511.html

> I'll go look for it or keep an eye out for it.

Sorry, but I havn't had chance to write to you about your financial

questions .... I'll try to compose something this weekend.

Here's wishing you and your husband and Wyatt much strength, wisdom

and courage.

Best regards.

Dave

(father of (21); PSC 07/03; UC 08/03)

[Guest guest]

Hi Meghan,

I responded to your post on the PSCmoms board. I don't post here often

but wanted to let you know that you are not alone with having a son

with PSC and FAP. My husband has a very strong family history of FAP

and so had his first colonoscopy at 30. He takes sulindac and has

yearly colonoscopies and it has been recommended that he have his

colon removed. He hasn't been willing to do that yet. My son has

inherited the FAP gene and also has short bowel syndrome (most of his

intestines removed including his ileocecal valve) and therefore has

major problems with colonic bacteria causing bacterial overgrowth. He

has had many ERCPs for strictures and stones obstructing his common

bile duct and had a series of stents replaced in his common bile duct

I am very interested in any info you have now and find out here and

elsewhere about how best to treat FAP and PSC together. My son doesn't

have UC but because he already has 3/4 of his small intestines removed

he has majorly compromised GI tract already even with 'just' short

bowel syndrome. My son has seen several GI and hepatologist

sub-specialists but none have been able/willing to put the big picture

together yet. My son is 10 and is one of my triplets - he has a

brother and a sister who could not be more different from eachother.

His brother and sister have not been tested for the FAP gene yet but

have had screening colonoscopies.

Lori