Re: High Dose Urso Study

June 10, 2008

,

I too have finished 5yrs with the study as of last September. I have not

recieved such news or an official letter, yet. But it is interesting that a

study coordinator told me a couple of weeks ago that the study is going for two

more years.

This news did not come as a shock to me too for the reasons that you have

mentioned. But i did not think that Mayo would not be recommending patients to

take Urso, anymore. I think i will still like to continue taking Urso,

prescribed by my GI, in a lower dose may be, not because that it has much

brought my enzymes that were skyrocketing before entering the study, into close

to normal, but because of some other benefits such as moving the bile.

Thank you, . And i will let you know if i do recieve a letter within the

coming days.

PSC/UC

From: jasonseakingpolo@...

Subject: High Dose Urso Study

To:

Date: Monday, June 9, 2008, 6:42 PM

-------While this news is dissapointing it does not come to a particular

shock to me since previous studies had been inconclusive at best. I

would be curious to know if other study participants have yet

received this news. Supposedly I will receive an official letter in

the coming days and be told if I was on " real " Urso or a placebo.

in Seattle

UC 1991, PSC 2001 - Stage IV

June 11, 2008

That is really disappointing. I had such high hopes - my husband's

labs, like everyone else's, have improved greatly on high dose Urso.

There was some suggestion in the literature, I thought, that Urso was

possibly more beneficial when started earlier in the progression of

the disease; do we know if those results took that into account? In

other words, is it still possible Urso is helpful if it is started

early on? Thanks,

Nina in Philly

June 11, 2008

I am new to PSC, diagnosed May 20th during my 2nd ERCP, to check things

out after a hospitalization for pancreatitis with ERCP in March. I had

multiple black stones removed in March, and actually had more stones

removed already during the 2nd ERCP.

So I am wondering what amount of URSO is high does, on May 20th my GI

started me on Urso Forte 500mg twice a day. I have not had a chance to

discuss my PSC yet because I couldn't get an appointment with my GI

until July 2nd, when I can discuss it with him.

I do not have the colon cancer issue, as I have not colon. It was

removed 25 years ago for ulcerative colitis. But I am lucky and have an

internal S-pouch.

Thanks in advance for help with this question,

Beth B (Thornton, CO)

June 11, 2008

,

My impression was that this was a fairly new development decided just

last week in a meeting of the principal study doctors. I also had

been told the study was extended an additional two years just a few

months ago so this was an unexpected change in direction.

in Seattle

>

> ,

>

> I too have finished 5yrs with the study as of last September. I

have not recieved such news or an official letter, yet. But it is

interesting that a study coordinator told me a couple of weeks ago

that the study is going for two more years.

>

> This news did not come as a shock to me too for the reasons that

you have mentioned. But i did not think that Mayo would not be

recommending patients to take Urso, anymore. I think i will still

like to continue taking Urso, prescribed by my GI, in a lower dose

may be, not because that it has much brought my enzymes that were

skyrocketing before entering the study, into close to normal, but

because of some other benefits such as moving the bile.

>

> Thank you, . And i will let you know if i do recieve a letter

within the coming days.

>

> PSC/UC

>

June 11, 2008

Beth,

High dose for the purposes of this study were considered to be 25

milligrams per kilogram of body weight.

in Seattle

>

> I am new to PSC, diagnosed May 20th during my 2nd ERCP, to check

things

> out after a hospitalization for pancreatitis with ERCP in March. I

had

> multiple black stones removed in March, and actually had more

stones

> removed already during the 2nd ERCP.

>

> So I am wondering what amount of URSO is high does, on May 20th my

GI

> started me on Urso Forte 500mg twice a day. I have not had a chance

to

> discuss my PSC yet because I couldn't get an appointment with my GI

> until July 2nd, when I can discuss it with him.

>

> I do not have the colon cancer issue, as I have not colon. It was

> removed 25 years ago for ulcerative colitis. But I am lucky and

have an

> internal S-pouch.

>

> Thanks in advance for help with this question,

>

> Beth B (Thornton, CO)

>

June 17, 2008

I just wanted to mention that when I saw Dr. Lindor a couple of weeks

ago when I was just diagnosed with PSC, he said that they don't give

Urso anymore because it wasn't shown to be effective for PSC. So the

results are already being implemented in clinical recommendations.

Ruth

UC 2000, Colectomy 2007, PSC 2008

> >

> > I realize I have not posted for awhile and for that I apologize

but

> I

> > do keep up with the messages when my schedule allows. I just

> wanted

> > to share some information I was given today as a participant in

the

> > Multi-Center High Dose Urso Study coordinated by The Mayo Clinic

> > (through Dr. Lindor). This study, originally slated for 5 years

(I

> > just finished year 5) was extended last year to gather more

data.

> > The original plan was to go another two years.

> >

> > I was just informed that effective immediately all patients are

> being

> > taken off of the Urso or Placebo doses they have been receiving.

> > This is due to there being no evidence that that high dose urso

was

> > having any benefit. They will continue to follow us for a year

to

> > study the impact to our lab results. I asked my study

coordinator

> if

> > they will continue to prescribe Urso to PSC patients outside of

the

> > study and it appears the conclusion is there is no tangible

benefit

> > and therefore they are not recommending PSC patients continue

> taking

> > Urso.

> >

> > While this news is dissapointing it does not come to a particular

> > shock to me since previous studies had been inconclusive at

best.

> I

> > would be curious to know if other study participants have yet

> > received this news. Supposedly I will receive an official letter

> in

> > the coming days and be told if I was on " real " Urso or a placebo.

> >

> > in Seattle

> > UC 1991, PSC 2001 - Stage IV

> >

>

June 17, 2008

I just wanted to mention that when I saw Dr. Lindor a couple of weeks

ago when I was just diagnosed with PSC, he said that they don't give

Urso anymore because it wasn't shown to be effective for PSC. So the

results are already being implemented in clinical recommendations.

Ruth

UC 2000, Colectomy 2007, PSC 2008

> >

> > I realize I have not posted for awhile and for that I apologize

but

> I

> > do keep up with the messages when my schedule allows. I just

> wanted

> > to share some information I was given today as a participant in

the

> > Multi-Center High Dose Urso Study coordinated by The Mayo Clinic

> > (through Dr. Lindor). This study, originally slated for 5 years

(I

> > just finished year 5) was extended last year to gather more

data.

> > The original plan was to go another two years.

> >

> > I was just informed that effective immediately all patients are

> being

> > taken off of the Urso or Placebo doses they have been receiving.

> > This is due to there being no evidence that that high dose urso

was

> > having any benefit. They will continue to follow us for a year

to

> > study the impact to our lab results. I asked my study

coordinator

> if

> > they will continue to prescribe Urso to PSC patients outside of

the

> > study and it appears the conclusion is there is no tangible

benefit

> > and therefore they are not recommending PSC patients continue

> taking

> > Urso.

> >

> > While this news is dissapointing it does not come to a particular

> > shock to me since previous studies had been inconclusive at

best.

> I

> > would be curious to know if other study participants have yet

> > received this news. Supposedly I will receive an official letter

> in

> > the coming days and be told if I was on " real " Urso or a placebo.

> >

> > in Seattle

> > UC 1991, PSC 2001 - Stage IV

> >

>

June 17, 2008

I just wanted to mention that when I saw Dr. Lindor a couple of weeks

ago when I was just diagnosed with PSC, he said that they don't give

Urso anymore because it wasn't shown to be effective for PSC. So the

results are already being implemented in clinical recommendations.

Ruth

UC 2000, Colectomy 2007, PSC 2008

> >

> > I realize I have not posted for awhile and for that I apologize

but

> I

> > do keep up with the messages when my schedule allows. I just

> wanted

> > to share some information I was given today as a participant in

the

> > Multi-Center High Dose Urso Study coordinated by The Mayo Clinic

> > (through Dr. Lindor). This study, originally slated for 5 years

(I

> > just finished year 5) was extended last year to gather more

data.

> > The original plan was to go another two years.

> >

> > I was just informed that effective immediately all patients are

> being

> > taken off of the Urso or Placebo doses they have been receiving.

> > This is due to there being no evidence that that high dose urso

was

> > having any benefit. They will continue to follow us for a year

to

> > study the impact to our lab results. I asked my study

coordinator

> if

> > they will continue to prescribe Urso to PSC patients outside of

the

> > study and it appears the conclusion is there is no tangible

benefit

> > and therefore they are not recommending PSC patients continue

> taking

> > Urso.

> >

> > While this news is dissapointing it does not come to a particular

> > shock to me since previous studies had been inconclusive at

best.

> I

> > would be curious to know if other study participants have yet

> > received this news. Supposedly I will receive an official letter

> in

> > the coming days and be told if I was on " real " Urso or a placebo.

> >

> > in Seattle

> > UC 1991, PSC 2001 - Stage IV

> >

>

June 17, 2008

he said that they don't give Urso anymore because it wasn't shown to be effective for PSC>>> But at least in my case it did thin the bile which probably prevented many bouts of cholangitis. The Urso didn't altogether prevent me from developing cholangitis though but my hep was content with the results enough that I got about 6 more years from my original liver. Hopefully the docs won't totally ignore the positive benefit that Urso has for the PSC patient and stop using it. Best regards, Barby - KS UC - 1965, ileostomy - 1972, BCIR (continent pouch) 1994, PSC - 1995, arthritis 2007, tx 11.29.07married 28 years , 5 sons, 2 daughters in law, 1 granddaughter, 1 grandbaby due 10/08 and 1 golden retriever

June 17, 2008

he said that they don't give Urso anymore because it wasn't shown to be effective for PSC>>> But at least in my case it did thin the bile which probably prevented many bouts of cholangitis. The Urso didn't altogether prevent me from developing cholangitis though but my hep was content with the results enough that I got about 6 more years from my original liver. Hopefully the docs won't totally ignore the positive benefit that Urso has for the PSC patient and stop using it. Best regards, Barby - KS UC - 1965, ileostomy - 1972, BCIR (continent pouch) 1994, PSC - 1995, arthritis 2007, tx 11.29.07married 28 years , 5 sons, 2 daughters in law, 1 granddaughter, 1 grandbaby due 10/08 and 1 golden retriever

June 17, 2008

he said that they don't give Urso anymore because it wasn't shown to be effective for PSC>>> But at least in my case it did thin the bile which probably prevented many bouts of cholangitis. The Urso didn't altogether prevent me from developing cholangitis though but my hep was content with the results enough that I got about 6 more years from my original liver. Hopefully the docs won't totally ignore the positive benefit that Urso has for the PSC patient and stop using it. Best regards, Barby - KS UC - 1965, ileostomy - 1972, BCIR (continent pouch) 1994, PSC - 1995, arthritis 2007, tx 11.29.07married 28 years , 5 sons, 2 daughters in law, 1 granddaughter, 1 grandbaby due 10/08 and 1 golden retriever

June 17, 2008

I read a study last year when I first tried URSO and it said the same

thing that this study is saying. I got the info from my local

pharmacist.

I tried it last year as a script from my local gi doc who diagnosed

me. But the doc at Baylor All Saints does not prescribe it for every

PSC pt. I did not tolerate it well last year, but just started it

again about a month ago after my doc at Baylor All Saints suggested it

because of increase BM's. I am doing very well on it and feel better

than I have in a long time.

PSC 5/07 Listed

June 17, 2008

I read a study last year when I first tried URSO and it said the same

thing that this study is saying. I got the info from my local

pharmacist.

I tried it last year as a script from my local gi doc who diagnosed

me. But the doc at Baylor All Saints does not prescribe it for every

PSC pt. I did not tolerate it well last year, but just started it

again about a month ago after my doc at Baylor All Saints suggested it

because of increase BM's. I am doing very well on it and feel better

than I have in a long time.

PSC 5/07 Listed

June 17, 2008

I am newly diagnosed with PSC 3/08 stage I and for the 1st time in 2.5 yrs my liver enzymes are normal .I've been on URSO for 3 mos ...I think I'm going to stay on it..I saw my GI guy today he says that is fine with him.

Re: High Dose Urso Study

> > > > > >>>

June 18, 2008

> When I told him that Dr. Chapman thought it should be in the

drinking water and I asked about the benefit urso has on colon

cancer, Lindor said there has been no clinical proof of that.

Hi Tim;

One of the best reviews I have seen on chemoprevention of colon

cancer in ulcerative colitis patients (with and without PSC) is this

one attachede below ... an article used for continuing medical

education (CME). Basically it encourages use of 5-aminosalicylates,

folic acid and ursodeoxycholic acid for colon cancer prevention.

Reference 19 in the reference list is one of the studies that support

use of ursodeoxycholic acid in colon cancer prevention in PSC

patients, and Dr. Lindor was one of the authors of this paper.

Therefore, I find it very odd that Dr. Lindor would say that there is

no clinical proof of cancer prevention by urso.

Best regards,

Dave R.

_____________________

Advances in Ulcerative Colitis - Volume 3 CME

Release Date: December 14, 2007; Valid for credit through December

14, 2008

http://www.medscape.com/viewarticle/566843

Expert Column - Ulcerative Colitis and Colorectal Cancer

Chemoprevention

Bret A. Lashner, MD

Introduction

Adherence to medical therapy is a major problem in ulcerative

colitis, with some estimates showing that up to 60% of patients fail

to take their medications as prescribed. Patients should be

encouraged by their physicians to adhere to their medical regimen due

to the favorable effect on their disease course.[1] What is often

overlooked is the possible cancer chemopreventive effect of these

medications. Hopefully, careful discussions regarding the beneficial

effects of therapies such as 5-aminosalicylic acid (5-

ASA/mesalamine), folic acid, and ursodeoxycholic acid, which include

their potential chemopreventive effects, will ultimately lead to

better adherence and improved patient outcomes.

Colorectal cancer is an important problem for ulcerative colitis

patients. The lifetime cumulative incidence has been estimated to be

between 5.5% and 13.5%.[2] While these rates are not very different

from those seen in the general population, the occurrence of cancer

at a young age makes age-specific relative risks at least 3 times the

baseline rate. The purported risk factors for cancer are extensive

disease, long duration of disease, primary sclerosing cholangitis

(PSC), family history of colorectal cancer, and possibly chronic

uncontrolled inflammation. In case-control studies, cancer

surveillance has been associated with a decreased risk of dying from

cancer, but still rates are sufficiently elevated to make cancer an

important concern.[3] Chemoprevention should be considered

complementary to cancer surveillance colonoscopy.

5-ASA Agents

Due to their anti-inflammatory effects, 5-ASA agents are the most

commonly used medications for the treatment of ulcerative colitis.

Indeed, 5-ASA therapy represents the current standard of care for

mildly to moderately active ulcerative colitis. This class of drugs

is also potentially useful for their chemopreventive effects, largely

through mechanisms complementary to anti-inflammatory effects. 5-ASA

inactivates reactive oxygen species, dampening the inflammatory

cascade and inactivating potential carcinogens. By suppressing

nuclear factor-kappaB (NF-kB) systems, 5-ASA decreases cytokine

production while increasing NF-kB-dependent apoptosis or programmed

cell death of cells with abnormal DNA. Additionally, 5-ASA is also

known to decrease interleukin (IL)-2 production, which in turn will

diminish clonal proliferation of T cells. Finally, 5-ASA activates

peroxisome proliferator-activator receptor (PPAR)-gamma, which

demonstrates both antiproliferative and anti-inflammatory effects.[4]

Six epidemiologic studies have specifically looked at the potential

of 5-ASA as a chemopreventive agent for colorectal cancer in

ulcerative colitis; 4 have shown a positive effect and 2 have shown

no effect.[5-10] A case-control study from Uppsala, Sweden, compared

102 ulcerative colitis patients with cancer to 196 matched controls

without cancer.[5] Results showed that the use of sulfasalazine, a

prodrug of 5-ASA, given for at least 3 months, was associated with a

significantly diminished risk of developing cancer (odds ratio [OR]

0.38, 95% confidence interval [CI] 0.20-0.69). Cigarette smoking and

active ulcerative colitis also had independent protective effects. In

a cohort study from Huddinge, Sweden, involving 143 patients with

ulcerative colitis who underwent regular colonoscopies and multiple

biopsies in a 20-year surveillance program, 36% developed cancer or

dysplasia over the course of follow-up.[6] Among patients who

received sulfasalazine for at least 6 months, there was a 34% rate of

colorectal dysplasia/cancer compared with a 44% rate among patients

who were taking sulfasalazine for less than 6 months (not

significant).

In a cohort study of colorectal cancer risk and treatment adherence

conducted at Leicester General Hospital in the United Kingdom

involving 175 patients with ulcerative colitis, 5.7% developed cancer

within the study period.[7] Among those patients who took

sulfasalazine for at least 6 months, the relative risk of developing

colorectal cancer was 0.11 (95% CI 0.04-0.28). Alternatively, a case-

control study from the United Kingdom comparing 102 ulcerative

colitis patients with cancer to matched controls found that

sulfasalazine had no significant protective effect; however, regular

therapy with other 5-ASA agents was associated with a chemopreventive

effect (OR 0.19, 95% CI 0.06-0.61).[8] In another study assessing

whether 5-ASA use can prevent the development of colorectal cancer in

patients with inflammatory bowel disease (IBD), Bernstein and

colleagues[9] identified 25 cases of IBD with a diagnosis of

colorectal cancer between the years 1997 and 2000 from the University

of Manitoba Inflammatory Bowel Disease Epidemiology Database. These

cases were compared to 348 matched controls (a control group of IBD

patients who did not develop colorectal cancer) extracted from this

same database. They found that among the cases of ulcerative colitis

with colorectal cancer, 45% were 5-ASA users, whereas only 25% of

controls were 5-ASA users (OR 0.48, 95% CI 0.07-3.25), and there was

no dose-response effect. Higher 5-ASA dosing did not incrementally

diminish the rate of colorectal cancer development. More recently, a

case-control study from the University of Chicago by Rubin and

colleagues[10] compared 26 ulcerative colitis patients with cancer or

dysplasia to 96 matched controls and found that use of 5-ASA >= 1.2 g

daily was associated with a significant chemopreventive effect (OR

0.28, 95% CI 0.09-0.85); there was a significant dose-response. A

meta-analysis examining these studies and others that have

principally looked at agents other than 5-ASA (such as folic acid,

immunosuppressives, and corticosteroids) has revealed a significant

chemopreventive effect of 5-ASA, even after adjusting for potential

confounders (OR 0.51, 95% CI 0.29-0.92) on colorectal cancer or

dysplasia.[11]

Therefore, even though the evidence for chemoprevention may be

equivocal, because 5-ASA is also effective in maintaining disease

remission, these agents should be recommended for long-term use in

patients with ulcerative colitis.

Folic Acid

Folic acid is essential for the regeneration of the amino acid

methionine, which is needed for both purine and pyrimidine

biosynthesis. Folic acid deficiency is associated with DNA

hypomethylation, aberrant DNA synthesis and repair, and decreased

apoptosis. Furthermore, folate-sensitive fragile sites exist on genes

that play an important role in carcinogenesis, particularly the p53

tumor suppressor gene. Folate deficiency may be associated with p53

mutations in ulcerative colitis patients,[12] who are especially

prone to folic acid deficiency due to intestinal losses, poor intake

of folic acid-containing foods such as leafy green vegetables, and

competitive inhibition of absorption from sulfasalazine.[13] Any

effects of folic acid deficiency have been partially ameliorated

since 1998 by the fortification of flour with folic acid in the

United States.

A case-control study involving 99 patients with pancolitis was

conducted to determine the effect of folate supplementation on the

risk of dysplasia or cancer in chronic ulcerative colitis.[13]

Results showed that among patients taking folic acid supplements, the

risk of developing dysplasia or cancer was diminished, although not

significantly (OR 0.38, 95% CI 0.12-1.20). Another case-control study

performed to better assess the association between folate

supplementation and the risk of developing dysplasia or cancer

included 67 ulcerative colitis patients enrolled in a cancer

surveillance program.[14] In this study, red blood cell folic acid, a

measure of medium-term stores, was found to be associated with a

chemopreventive effect (OR for each 10-ng/mL increase in red blood

cell folate: 0.82, 95% CI 0.68-0.99). Given that these 2 case-control

studies had suggested the potential protective effect of folate

against neoplasia in ulcerative colitis, a historical cohort study

was undertaken to better define this association.[15] This 98-patient

cohort study found a nonsignificant protective effect of folic acid

supplementation on the risk of cancer or dysplasia (relative risk

0.72, 95% CI 0.28-1.83), but the relative risk for folic acid

supplementation on the risk of neoplasia showed a dose-response

effect. Finally, in a cohort of 95 patients with long-standing

ulcerative colitis who were followed in a cancer surveillance program

using immunohistochemical staining for p53 mutations as a

complementary test for dysplasia, p53 suppressor gene mutations were

found to be associated with cancer or dysplasia (relative risk 4.53,

95% CI 2.16-9.48); folic acid supplementation had a protective effect

for p53 mutations (relative risk 0.97, 95% CI 0.94-1.00).[12]

Once again, while the evidence may be weak, because folic acid is

inexpensive, safe, and recommended for prevention of atherosclerotic

heart disease, it should also be recommended for long-term use in

patients with IBD.

Ursodeoxycholic Acid

Ursodeoxycholic acid (UDCA) is often used to improve symptoms and

biochemical abnormalities in patients with PSC. Indeed, recent

studies have implicated PSC as a risk factor for colorectal cancer in

ulcerative colitis.[16] Theoretically, UDCA may be chemopreventive

for colorectal cancer in patients with ulcerative colitis. In a

cohort study involving 132 ulcerative colitis patients with PSC and

196 ulcerative colitis controls, the risk of developing colorectal

cancer or dysplasia was significantly increased among PSC patients

(relative risk 3.15, 95% CI 1.37-7.27).[17] It is interesting to note

that in this study, all of the excess cancer risk pertained to cancer

found proximal to the splenic flexure. In theory, carcinogenic

secondary bile acids, such as deoxycholic acid (which is abnormally

high in patients with cholestasis), are presented to the right side

of the colon in higher concentrations than the left side. Reducing

the concentration of these secondary bile acids with UDCA could have

chemopreventive effects.

To assess the relationship between UDCA use and colonic dysplasia in

patients with ulcerative colitis, Tung and colleagues[18] conducted a

study involving 59 ulcerative colitis patients with PSC who were

undergoing colonoscopic surveillance; 69% were on UDCA. Dysplasia was

found in 32% of the UDCA users and in an exceedingly high 72% of UDCA

nonusers (OR 0.14, 95% CI 0.03-0.64). In a 52-patient, randomized,

placebo-controlled clinical trial (the only randomized clinical trial

done to test for cancer-chemopreventive effects of an agent in

ulcerative colitis) designed to test the effect of UDCA use on liver

disease progression in PSC, 10% of patients randomized to UDCA

developed dysplasia and 35% of placebo-treated patients developed

dysplasia (relative risk 0.26, 95% CI 0.07-0.99).[19] Finally, in the

only negative study in this setting, 120 PSC patients with ulcerative

colitis, 23% of whom were treated with UDCA, were followed by Wolf

and colleagues.[20] Over the course of follow-up, 28.6% of UDCA-

treated patients developed cancer or dysplasia compared with 29.3% of

patients who did not receive UDCA (adjusted relative risk 0.65, 95%

CI 0.27-1.55).

Once again, although the evidence may be conflicting, because UDCA is

recommended for the treatment of PSC, its use should also be

encouraged for its possible cancer-chemopreventive effects.

Conclusion

On the basis of the evidence presented here, patients with ulcerative

colitis should be taking a long-term 5-ASA agent for its maintenance

effects as well as for its potential cancer-chemopreventive effect.

Folic acid supplementation, either 1 mg daily as a sole supplement or

0.4 mg daily in a multivitamin, is also recommended to be certain

that ulcerative colitis patients, who are prone to folic acid

deficiency, are replete and can benefit from the potential

chemopreventive effect. Likewise, ulcerative colitis patients with

PSC should be taking UDCA both for the treatment of their liver

disease and for possible colon cancer chemoprevention. Certainly, the

cancer-chemopreventive effects associated with the use of these

medications are insufficient to obviate the need for cancer

surveillance colonoscopy. As underscored by the preceding discussion,

the studies in cancer chemoprevention supporting these

recommendations are currently weak and inconsistent -- however, the

many potential benefits associated with the use of these agents

should prompt physicians to strongly encourage their use in the

setting of ulcerative colitis.

References

1. Kane SV, Cohen RD, Aikens JE, Hanauer SB. Prevalence of

nonadherence with maintenance mesalamine in quiescent ulcerative

colitis. Am J Gastroenterol. 2001;96:2929-2933.

2. Karlen P, Lofberg R, Brostrom O, Leijonmarck CE, Hellers G,

Persson PG. Increased risk of cancer in ulcerative colitis: a

population-based cohort study. Am J Gastroenterol. 1999;94:1047-1052.

3. Eaden J, Abrams K, Ekbom A, E, Mayberry J. Colorectal

cancer prevention in ulcerative colitis: a case-control study.

Aliment Pharmacol Ther. 2000;14:145-153.

4. Allgayer H. Review article: mechanisms of action of mesalazine in

preventing colorectal carcinoma in inflammatory bowel disease.

Aliment Pharmacol Ther. 2003;18:10-14.

5. Pinczowski D, Ekbom A, Baron J, et al. Risk factors for colorectal

cancer in patients with ulcerative colitis. Gastroenterology.

1994;117-120.

6. Lindberg BU, Broome U, Persson B. Proximal colorectal dysplasia or

cancer in ulcerative colitis. Dis Colon Rectum. 2001;44:77-85.

7. Moody GA, Jayanthi V, Probert CS, et al. Long-term therapy with

sulfasalazine protects against colorectal cancer in ulcerative

colitis. Eur J Gastroenterol Hepatol. 1996;8:1179-1183.

8. Eaden J, Abrams K, Ekbom A, et al. Colorectal cancer prevention in

ulcerative colitis. Aliment Pharm Ther. 2000;14:145-153.

9. Bernstein CN, Blanchard JF, Metge C, Yogendran M. Does the use of

5-aminosalicylic acid in inflammatory bowel disease prevent the

development of colorectal cancer? Am J Gastroenterol. 2003;98:2784-

2788.

10. Rubin DT, LoSavio A, Yadron N, et al. Aminosalicylate therapy in

the prevention of dysplasia and colorectal cancer in ulcerative

colitis. Clin Gastroenterol Hepatol. 2006;4:1346-1350.

11. Velayos FS, Terdiman JP, Walsh JM. Effect of 5-aminosalicylate

use on cancer and dysplasia risk: a systematic review and meta-

analysis of observational studies. Am J Gastroenterol. 2005;100:1345-

1353.

12. Lashner BA, Shapiro BD. Husain A, Goldblum JR. Evaluation of the

usefulness of testing for p53 mutations in colorectal cancer for

ulcerative colitis. Am J Gastroenterol. 1999;94:456-462.

13. Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate

supplementation on the incidence of dysplasia and cancer in

ulcerative coiltis. Gastroenterology. 1989;97:255-259.

14. Lashner BA. Red blood cell folate is associated with the

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