Sunday, August 19, 2007

Predicting the progression of Peyronie's: An utrasound study

It's a mark of how under-studied Peyronie's has been that we're only now beginning to understand the course of the disorder (see also). These Greek researchers divided their study group up based on initial ultrasound, then followed their course for a year without intervention (emphases mine):
The Natural History of Peyronie's Disease: An Ultr...[Eur Urol. 2007] - PubMed Result

Eur Urol. 2007 Jul 17
The Natural History of Peyronie's Disease: An Ultrasonography-Based Study.
Bekos A, Arvaniti M, Hatzimouratidis K, Moysidis K, Tzortzis V, Hatzichristou D.
Center for Sexual and Reproductive Health and 2nd Department of Urology, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Greece.

OBJECTIVES: To define ultrasonographic patterns reflecting different states of Peyronie's disease (PD) and to use them to evaluate the natural history of the disease.

MATERIAL AND METHODS: Diagnosis of PD was based on medical and sexual history, physical examination, intracavernosal injection test, and penile ultrasonography. Patients with penile fracture history were excluded from the study. Three groups were formed according to ultrasonographic patterns: solitary hyperechoic lesion without acoustic shadow (group A), moderately hyperechoic multiple scattered calcified lesions with acoustic shadows (group B), dense calcified hyperechoic plaque with acoustic shadow (group C). All patients entered a watchful waiting protocol for 1 yr followed by a new penile ultrasonography.

RESULTS: Ninety-five 95 patients with PD were included in the study (mean age, 57.2+/-9.1 yr; mean duration of disease, 12.9+/-8.9 mo). Risk factors associated with cardiovascular disease were present in 79 of 95 patients (83.16%). Eleven (11.6%), 35 (36.8%), and 49 (51.6%) patients were classified into groups A, B and C, respectively.

At the end of the study, in group A, reduction of fibrotic lesions and curvature angle was noticed in 9 of 11 (81.8%) patients, whereas plaque formation was noticed in 2 of 11 (18.2%) patients. In group B, plaque and curvature reduction was noticed in 15 of 35 (42.9%) and 12 of 35 (34.3%) respectively, whereas in the rest a dense calcified plaque was noticed. In group C, no ultrasonographic evidence of improvement was noticed; curvature angle was reduced in 4 of 49 (8.2%), owing to the extension of the plaque circumferentially. Significant hemodynamic changes were noticed at the two time points tested (30.53% diagnosed with vascular disease at baseline vs. 46.32% at the end of the study, p=0.03).

CONCLUSIONS: Corporal ultrasonography in patients with PD allows objective evaluation and classification of disease. The density of echogenic areas and presence of acoustic shadows are predictors of disease stability.

PMID: 17673362 [PubMed - as supplied by publisher]
If this holds up urologists will be better decide when aggressive treatment is indicated. The overall news was not encouraging and is line with other recent studies of disease course. This was an older population and thus might be expected to have less aggressive disease, but in fact only 11% fell into the "good" group at the start of the study. Half were in the "bad" group at the start and none of them improved.

Peyronie's Proteomics

A few weeks ago I wrote:
Peyronie's Disease - the blog: Proteomics in Peyronie's Disease - including a review of gene profiling in PD: "As I wrote a couple of days ago, even an area as understudied as Peyronie's can advance quickly when new instruments are brought to bear on old questions. Proteomics is all the rage in our post-genomic era, but besides the faddish topic the article claims to have reviewed the full literature on gene profiling in PD (of course that probably took about 3 hours)."
Coincidentally, I've since had to do a review of protein network research and disease definition.

I now understand that one of the promises of protein networks is the ability to redefine diseases, which includes grouping differing syndromes into single disease classes and dividing a disease into subtypes -- or eliminating the disease/syndrome altogether. Protein networks, in other words, may do for our understanding of disease in humans what DNA research has done for defining and redefining species.

So this research may, for example, tell us if there really are important relationship between Peyronie's, Duputren's and other disorders of fibrosis.

Clostridial Collagenase treatment for Peyronie's, Dupytren's and Frozen Shoulder syndrome

I usually don't pay attention to press releases on clinical trials -- they're fishing expeditions for investors and/or speculators. This one caught my eye because of the focus on several diseases of pathologic fibrosis:
Auxilium Pharmaceuticals, Inc. Receives Clearance to Resume Clinical Trials for XIAFLEX(TM)

Auxilium Pharmaceuticals, Inc. (Nasdaq: AUXL) today announced that the Company has received clearance from the U.S. Food and Drug Administration ('FDA') to resume its phase III clinical trials for XIAFLEX (clostridial collagenase for injection), formerly referred to as AA4500, in the treatment of Dupuytren's contracture.
... The Company plans to initiate a pivotal double-blind trial in the U.S., a double-blind trial in Australia, and two open label trials that along with previously conducted trials will serve as the basis for the Biologics License Application ('BLA') for marketing approval from the FDA....

... Auxilium has four projects in clinical development. XIAFLEX(TM) (clostridial collagenase for injection), formerly referred to as AA4500, is in phase III development for the treatment of Dupuytren's contracture and is in phase II development for the treatment of Peyronie's disease and Frozen Shoulder syndrome (Adhesive Capsulitis).

Saturday, August 4, 2007

Dupuytren's disease: does it really affect 25% of northern Europeans?

We know Peyronie's Disease is more common than once though among white males over age 50, and there's long been thought to be an association with Dupuytren's contracture. So I've been learning a bit about Dupuytren's. I was very surprised to see a news article claiming that 25% of western European men will develop Dupuytren's Disease. That seemed absurdly high. I finally got around to researching that number (italics mine)

Epidemiology of Dupuytren's disease: clinical, ser...[J Clin Epidemiol. 2000] - PubMed Result

1: J Clin Epidemiol. 2000 Mar 1;53(3):291-6. Epidemiology of Dupuytren's disease: clinical, serological, and social assessment. The Reykjavik Study. Gudmundsson KG, Arngrímsson R, Sigfússon N, Björnsson A, Jónsson T. The Health Care Centre, 540, Blonduos, Iceland.

Dupuytren's disease or palmar fibromatosis is a common disabling hand disorder, mainly confined to Caucasians of northwestern European origin. The prevalence of Dupuytren's disease and possible risk factors related to the disease were evaluated in a random sample of 1297 males and 868 females, aged 46 to 74 years. Blood samples were collected and biochemical parameters were evaluated. The possible relation between the disease and clinical, social, and biochemical parameters were estimated with age-adjusted univariate logistic regression analysis. Altogether 19.2% of the males and 4.4% of the female participants had clinical signs of Dupuytren's disease. The prevalence increased with age, from 7.2% among males in the age group 45-49 years up to 39.5% in those 70-74 years old. The more severe form of the disease, finger contractures, was found in 5.0% of the men and 1.4% had required operation, while this was rarely seen among women. In men elevated fasting blood glucose (P < 0.04), low body weight, and body mass index were significantly correlated with the presence of the disease (P < 0.001). Dupuytren's disease was common among heavy smokers (P = 0.02) and those having manual labor as occupation (P = 0.018). These results show that Dupuytren's disease is common in the Icelandic population and occupation and lifestyle seem to be related to the disease.

So the answer is that 25% is perhaps true for north-western Caucasian Europeans, but it refers to early signs of the disease. The prevalence of contractures in this population is only 5%, and Scandinavians appear to have the highest risk of all. On the other hand I was unable to find any literature suggesting Scandinavians were particularly prone to Peyronie's disease. The number is misleading in the context of the news article.