Has there been developed any treatment for Dupuytrens Contracture and
Plantar Fibromatosis (NOT Plantar Fasciaitis)?    I.e., Either:  (1)
Removing lumps without surgery, or   (2) Preventing growth of existing
& emergence of
new lumps, or  (3) If surgery is the only treatment, has there been
developed a way to undergo surgery WITHOUT spawning multiple new
lumps?

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Request for Question Clarification by jbf777-ga on 18 Jun 2003 19:37 PDT

You're looking specifically for an answer with regard to both conditions?

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Clarification of Question by lumpy3721-ga on 19 Jun 2003 05:36 PDT

I would be happy with a response regarding either or both conditions. 
The pathology of the conditions (as well as Peyronies Disease - but
thank heaven I don't have a penis) are of course virtually identical;
the only significant difference is in affected limb.  I realize,
however, that researchers tend to focus on one location when applying
for grant funding, so research may have found a treatment for e.g.
Dupuytrens that hasn't be tested/proven on the other extremities.   So
the question applies to either or both - Dupuytrens or Plantar
Fibromatosis:  Is there treatment for:  Preventing growth of existing
& emergence of new lumps, or Removing lumps without surgery, or
Preventing the spawning of multiple new lumps as a result of surgery
??

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Request for Question Clarification by jbf777-ga on 19 Jun 2003 09:16 PDT

You're using the term lumps exclusively; however, you're aware that a
good portion of the ailment is in the contracture of the "bands?"  Are
you only interested in lump removal?

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Clarification of Question by lumpy3721-ga on 20 Jun 2003 03:29 PDT

Yes, my question is very clearly directed to the issue of lumps.  At
this point, the lumps impact normal functioning, restricting movement
in some situations and imposing pain/discomfort in others.  The lumps
will of course ultimately progress to the point of contracting the
"bands".  In one location contracture has begun; in other locations
cramping is often experienced.  So are you suggesting I should simply
ignore the discomfort, ugly appearance, and distortion caused by the
lumps and wait until the bands contract, and then cut the bands to
relieve the contracture?  Isn't it far more invasive and radical to
cut bands than it is to remove lumps before they invade the bands?

Hello lumpy3721,

I searched on the Medline database 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
to see if there have been reports in the medical literature that might
provide some answers to your query.  I found many more reports about
Dupuytren’s disease than about plantar fibromatosis.

Here follows a list of articles of potential relevance, together with
my own summary and/or extracts from the authors’ summaries.  The URLs
lead to the Medline entry for the article with authors’ summaries.

With respect to DUPUYTREN’S DISEASE:

Steroid treatment has been reported to reduce the rate of fibroblast
cell proliferation and increase the rate of apoptosis (programmed cell
death) in nodules of Dupuytren's disease.  Fibroblasts are the cells
making up the fibrous tissue of the nodules. The treatment also
increased the rate of apoptosis of inflammatory cells in the nodules:

J Hand Surg [Br]. 2002 Jun;27(3):270-3. 
The effect of steroids on Dupuytren's disease: role of programmed cell
death.
D Meek RM, McLellan S, Reilly J, Crossan JF.
University Department of Orthopaedics, Western Infirmary, Glasgow,
Scotland, UK.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12074617&dopt=Abstract

Another report of promising results with steroid treatment:

J Hand Surg [Am]. 2000 Nov;25(6):1157-62. 
The injection of nodules of Dupuytren's disease with triamcinolone
acetonide.
Ketchum LD, Donahue TK.
Department of Surgery, Menorah Medical Center, Overland Park, KS, USA.
“Over a 4-year period 63 patients (75 hands) with Dupuytren's nodules
were treated with a series of injections with the steroid
triamcinolone acetonide directly into the area of disease…. After an
average of 3.2 injections per nodule 97% of the hands showed
regression of disease as exhibited by a softening or flattening of the
nodule(s). Although some patients had complete resolution of the
nodules, most experienced definite but incomplete resolution of the
nodules in the range of 60% to 80%. Although a few patients did not
experience recurrence or reactivation of the disease in the injected
nodules or development of new nodules, 50% of patients did experience
reactivation of disease in the nodules 1 to 3 years after the last
injection, necessitating 1 or more injections.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11119679&dopt=Abstract

Radiotherapy has been reported to prevent disease progression in
early-stage disease:

Strahlenther Onkol. 2001 Nov;177(11):604-10.    
[Radiotherapy of early stage Dupuytren disease. Long-term results
after a median follow-up period of 10 years]
[Article in German]
Adamietz B, Keilholz L, Grunert J, Sauer R.
Klinik und Poliklinik fur Strahlentherapie der Universitat
Erlangen-Nurnberg, Erlangen.
“Between 1982 and 1994, 99 patients (176 hands) received orthovoltage
radiotherapy…. The long-term outcome was analyzed at last follow-up
between July and November 1999. The median follow-up was 10 years
(range 7-18 years)… In Stage N 84% and Stage N/I 67% of cases remained
stable. 65% of the cases in Stage I and 83% in Stage II showed
progressive nodules and cords. In case of progression we saw no
complications after a second radiotherapy or salvage operation.
CONCLUSION: Radiotherapy effectively prevents disease progression for
early stage Dupuytren's contracture (Stage N, N/I). Moreover, in case
of disease progression despite radiotherapy salvage surgery is still
feasible.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11757183&dopt=Abstract

and also (the abstract to this paper defines the classification of
disease stage that is also used in the above reference):
Int J Radiat Oncol Biol Phys. 2001 Mar 1;49(3):785-98. 
Radiotherapy optimization in early-stage Dupuytren's contracture:
first results of a randomized clinical study.
Seegenschmiedt MH, Olschewski T, Guntrum F.
Department of Radiation Oncology, Therapeutic Radiology and Nuclear
Medicine, Alfried Krupp Krankenhaus, Alfried Krupp Str. 21, 45117
Essen, Germany
“Herein, the 1-year results of a prospective randomized trial are
presented which compared two different RT dose concepts with each
other. METHODS: 129 patients (67 males; 62 females) were entered in
this study: 69 had bilateral and 60 uni-lateral involvement of DC
accounting for 198 irradiated hands. According to Tubiana's
classification, 73 hands had Stage N (nodules/cords, no extension
deficit = flexion deformity), 61 had Stage N/I (< or = 10 degrees
deficit), 59 had Stage I (11-45 degrees deficit), and 5 had Stage II
(46-90 degrees deficit) DC…. Both prophylactic RT concepts have been
well accepted and tolerated by patients. Within the first year, they
were equally effective to prevent further disease progression of DC
and obtain considerable symptomatic improvement. Although 1-year
results suggest similar response rates for both treatment groups,
long-term FU [follow-up] of > 5 years has to be awaited for final
assessment and recommendation of an optimized RT treatment schedule.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11172962&dopt=Abstract

Tamoxifen was found to decrease the growth in culture of fibroblasts
from tissue affected by Dupuytren’s disease and to also to decrease
the production of TGF (tumor growth factor) beta-2 by the fibroblasts.
 TGF beta-2 is thought to play a key role in the progression of
Dupuytren’s disease. Please note, however, that this was very much an
experimental in vitro study. However, tamoxifen is used in the
treatment of Peyronie’s Disease, although only to reduce pain:

Surg Res. 2002 Apr;103(2):146-52
Tamoxifen decreases fibroblast function and downregulates TGF(beta2)
in Dupuytren's affected palmar fascia.
Kuhn MA, Wang X, Payne WG, Ko F, Robson MC.
Department of Veterans Affairs Medical Center, Institute of Tissue
Regeneration, Repair, and Rehabilitation, Bay Pines, Florida 33744,
USA.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11922728&dopt=Abstract

With respect to treatment of the contractures themselves, a clinical
trial with collagenase has shown encouraging results:

J Hand Surg [Am]. 2002 Sep;27(5):788-98. 
Collagen as a clinical target: nonoperative treatment of Dupuytren's
disease.
Badalamente MA, Hurst LC, Hentz VR.
Department of Orthopaedics, State University of New York at Stony
Brook, Health Science Center, Stony Brook, NY 11794, USA.
“In a series of controlled phase-2 clinical trials, excessive collagen
deposition in Dupuytren's disease has been targeted by a unique
nonoperative method using enzyme (Clostridial collagenase) injection
therapy to lyse and rupture finger cords causing metacarpophalangeal
and/or proximal interphalangeal joint contractures….  The results of
these studies indicate that nonoperative collagenase injection therapy
for Dupuytren's disease is both a safe and effective method of
treating this disorder in the majority of patients as an alternative
to surgical fasciectomy. Phase-3 efficacy trials are now being planned
to further develop and test this method under Food and Drug
Administration regulatory guidelines.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12239666&dopt=Abstract

I looked on the National Library of Medicine database of current
trials.  One US trial that is currently recruiting will investigate
the effect of collagenase, but only when used after surgery to deal
with residual disease:
“Phase II Randomized Study of Collagenase in Patients With Residual
Type Dupuytren's Disease”
http://clinicaltrials.gov/ct/show/NCT00004409?order=1 

With respect to PLANTAR FIBROMATOSIS, there were many fewer articles,
and no new ones about treatment strategies.

A 1998 study of fibromatoses at various sites mentions the possibility
of radiotherapy with or without surgery:

Int J Radiat Oncol Biol Phys. 1998 Feb 1;40(3):637-45. 
Individualizing management of aggressive fibromatoses.
Spear MA, Jennings LC, Mankin HJ, Spiro IJ, Springfield DS, Gebhardt
MC, Rosenberg AE, Efird JT, Suit HD.
Department of Radiation Oncology, Massachusetts General Hospital,
Harvard University Medical School, Boston 02114, USA.
“These results are consistent with those found in the relevant
literature. They support primary resection with negative margins when
feasible. Radiation is a highly effective alternative in situations
where surgery would result in major functional or cosmetic defects.
When negative surgical margins are not achieved in recurrent tumors,
radiation is recommended. Perioperative radiation should be considered
in other high-risk groups (recurrent disease, positive margins, and
plantar tumors in young patients).”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9486614&dopt=Abstract

Other relatively recent articles (last 10 years) that deal with
treatment refer to surgery, with one exception.  However, this
exception reports the failure of steroid treatment to cause
improvement in a case which resulted in the formation of ulcers on the
skin as well as internal nodules:

Hautarzt. 2001 Mar;52(3):236-9. 
[Plantar fibromatosis with marked cutaneous involvement]
[Article in German]
de Almeida HL Jr, Wolter M, Neugebauer MG, Neugebauer S.
Medizinische Fakultat der Bundesuniversitat Pelotas, Brasilien.
“Intralesional therapy with corticosteroids did not reduce the
lesions. After surgical treatment, the lesions recurred.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11284070&dopt=Abstract


A method using laser surgery is described as an alternative to
traditional incision methods:

Clin Podiatr Med Surg. 1992 Jul;9(3):617-32. 
Carbon dioxide laser excision of benign pedal lesions.
McDowell BA.
“The CO2 laser is a very important tool to remove benign pedal
lesions. It certainly is not the only method, but once the technique
is developed by the surgeon, it becomes easier to remove these lesions
and, consequently, the results become better…. This is also true with
fibromas because many types of fibromas would require suturing that
would create an inconvenience for the patient. With the use of the
laser, sutures are not required and the patients recover much faster.
In dealing with plantar fibromatosis, ganglionic cysts, and lipomas,
the convalescence is probably about the same with CO2 laser as with
conventional removal, especially when deep resection is necessary and
suturing of the skin is required. With plantar fibromata surgery, the
resultant long-term scarring is much less with the CO2 laser,
especially when followed up with the appropriate injectables.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1393984&dopt=Abstract

MeSH does not have a separate index term for Plantar Fibromatosis,
classifying it under the more-general term “fibroma”.  I used
“fibroma” as a MeSH term in a further search (details and rationale in
Search Strategy description below).  I did this to see if there were
any other therapeutic approaches, other than those listed above, being
investigated for similar diseases.

One review mentions a number of therapeutic strategies that have been
tried in various related conditions, with respect to controlling
recurrence after surgery. Steroids (hormonal agents) are cited as
giving promising results, also interferon, NSAIDS (non-steroidal
anti-inflammatory drugs) and cytotoxic drugs, of the sort used in
cancer chemotherapy (obviously the resulting side effects would make
this a treatment only for the most serious cases). However, the
authors conclude that as yet insufficient studies have been done to
allow a proper evaluation of these approaches.

Ann Oncol. 2003 Feb;14(2):181-90. 
The pharmacological treatment of aggressive fibromatosis: a systematic
review.
Janinis J, Patriki M, Vini L, Aravantinos G, Whelan JS.
Social Security Organization Oncology Center, Kifissia, Greece
“Despite the use of surgery and radiotherapy, 20-35% of patients with
aggressive fibromatosis (AF) will have local recurrence. The purpose
of this review was to collect and analyze all available information
regarding the role of non-cytotoxic and cytotoxic chemotherapy in AF
that has been accumulated over the past few decades…. Most commonly
used agents include hormonal agents, non-steroidal anti-inflammatory
drugs (NSAIDs), interferons and cytotoxics. The literature data
support the use of hormonal agents. Several questions, however, remain
unresolved, such as which is the most suitable endocrine manipulation
and what is the optimal dose and duration of treatment. NSAIDs and
interferons have demonstrated activity against AF either alone or in
combination with hormone therapy or chemotherapy but the precise
mechanism of action is still unknown. Finally, there is growing
evidence in the literature that chemotherapy is effective against AF
with almost one in two patients being likely to respond….  However,
the lack of sufficient patient numbers and randomized trials
compromises the validity of the reported results and mandates further
investigation with properly designed prospective studies including
larger patient numbers, with main end points to include not only tumor
response rate and survival but also quality-of-life issues.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12562642&dopt=Abstract

There is currently a European clinical trial on the efficacy of
radiotherapy against aggressive fibromatosis at any site:
“Radiation Therapy in Treating Patients With Aggressive Fibromatoses”
http://clinicaltrials.gov/ct/show/NCT00030680?order=1

Search strategy: I searched on the Medline database using the MeSH
indexing system to narrow down the search to therapeutic approaches:
Dupuytren’s search:  "Dupuytren's Contracture"[MAJR] AND ("Dupuytren's
Contracture/drug therapy"[MAJR] OR "Dupuytren's Contracture/prevention
and control"[MAJR] OR "Dupuytren's Contracture/therapy"[MAJR])
Plantar Fibromatosis search: MeSH does not have a separate index term
for this condition, classifying it under the more-general term
“fibroma”. I therefore searched simply on “plantar fibromatosis”,
anticipating that there would not be a large number of records to
review (there were 109 altogether).
I also searched with the MeSH term “fibroma”: ("Fibroma/drug
therapy"[MAJR] OR "Fibroma/prevention and control"[MAJR] OR
"Fibroma/therapy"[MAJR])
In addition, I searched http://clinicaltrials.gov for news of any
ongoing clinical trials.

Please do not hesistate to request clarification if any of the above
is unclear.

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Clarification of Answer by tehuti-ga on 20 Jun 2003 06:37 PDT

The advertisements that appear above this question include one about
the use of topical verapamil in Dupuytren's disease.  I looked at the
site http://www.topicalverapamil.com/  It does say there that such use
of verapamil has not been approved by the FDA and can therefore be
given on an off-label basis only.  The studies cited on the site refer
only to Peyronie's disease.

However, searching on this topic on Medline, I did find a reference to
an in vitro study, which suggests verapamil might be a possible
strategy, although it is curious that this study was published six
years ago and no further work appears to have been done:

J Hand Surg [Am]. 1996 Nov;21(6):1065-70. 
Pharmacologic regulation of Dupuytren's fibroblast contraction in
vitro.
Rayan GM, Parizi M, Tomasek JJ.
Department of Orthopaedic Surgery, University of Oklahoma Health
Sciences Center, Oklahoma City, USA.
"Dupuytren's disease is associated with contraction of specialized
fibroblasts present in the diseased palmar fascia... These findings
provide a rational basis for investigating further the clinical use of
the calcium channel blockers nifedipine or verapamil and
prostaglandins E1 and E2 to control Dupuytren's disease and possibly
other fibrotic conditions."

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Request for Answer Clarification by lumpy3721-ga on 21 Jun 2003 05:01 PDT

Thank you very much for your fine work, tehuti-ga.  You found great
information that eluded my research efforts.  I have two comments (not
"request for clarification"):
 (1) The trick now is to locate a physician (especially difficult in
Central Florida, my residence) who is willing to try one of these
approaches, rather than simply "cut".  I have had three disastrous
surgeries on one foot, and refuse to take the chance again -
especially on my hands! (I have "lumps" - continually
growing/increasing - on both hands & both feet)  Physicians are
notoriously arrogant, believe they have perfect knowledge, and reject
all other approaches (especially e.g. Eastern or alternative
medicine!) as quackery.
 (2) I dealt with the company that sells topical verapamil, and became
a little suspicious as you did.  Not only because they don't seem to
have made forward progress in the six years since original study, but
also because of the manner in which they dealt with me -- they seemed
to "hustle" me, wrote me a letter saying that they had a prescription
waiting for me that my physician had written -- but when I called them
they quickly changed their story to "we sent a letter to your
physician, but you have to get him to authorize a prescription".

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Clarification of Answer by tehuti-ga on 21 Jun 2003 05:22 PDT

One possible route you could try is to contact the authors of some of
the cited papers. I have given the postal address wherever it was
provided in the Medline record.  If you follow the URL to the record,
you will also find that a number of them contain email addresses. Some
of these authors might be able to give you the name of a colleague in
your region who is open to these non-surgical approaches.  However, it
might also be necessary for you to explore the feasibility of
travelling further afield, whether in the US or abroad to obtain the
types of treatment you prefer. The radiotherapy approach,
unfortunately, seems to be being pursued most actively in Germany.

Your experiences with the company certainly confirm my suspicions. I
was also unhappy about the fact that despite the claims that this
treatment works for a number of connective tissue disorders, the
studies they cited referred only to one condition.

Thank you once again for your generosity. I sincerely hope you will
succeed in finding a happy outcome.
Tehuti

I am overwhelmed by the generosity of your tip. Thank you, very, very much. Tehuti