Experience of Carboxytherapy in Conservative Treatment of Peyronie’s disease

Fabrizio Muzi1, Daniele D'andria2, Giulio Baffigo3, Francesco Corvese3, Giampaolo Delicato3, Alessandro Perla3, Stefano Signore3, Edoardo Tartaglia3, Giuseppe Montagna3, Gaetano Tati4
  • 1 Ospedale Sant'Eugenio - U.O.C. Oncologia (Roma)
  • 2 Università di Tor Vergata (Roma)
  • 3 Ospedale Sant'Eugenio - U.O.C. Urologia (Roma)
  • 4 Ospedale Sant'Eugenio - U.O.C. Urologia Oncologica (Roma)

Objective

Peyronie’s disease (PD) is an acquired disorder of tunica albuginea characterized by penis plaques of fibrous tissue often associated with erectile dysfunction (ED). Activated inflammatory cells produce oxygen radicals (ROS) initiating a chain of biochemical events leading to fibroblast proliferation and collagen apposition. The principal protein involved is NF-kB (1)
Carboxytherapy refers to the administration of CO2 for therapeutic purposes. It has been shown that CO2 has cell interaction in regulating factors of tissue perfusion. Nowadays CO2 is used as anti-aging treatment, for cellulite of all grades, for wrinkles reduction and for stretch marks. (7)
Clinical studies have indicated that altered tissue CO2 levels can impact upon inflammation progression. (3)
The objective of the study is to demonstrate that CO2 subcutaneous subministration, carboxytherapy, could realize sensibile reduction of fibrosis and oxidative phenomena of ROS in PD, reducing sexual discomfort of patients. Carboxytherapy could be employed as new easy method and free risk conservative treatment for PD.

Methods and results

We have recruited 15 patients, aged from 40 to 60 years old, affected by PD until 1 year. We have used IIEF questionary and we have studied ultrasound plaque's morphology before and after treatments to assess patients. We have injected  by specific medical device 500cc of sterile Medical CO2 for 10-15 weekly applications in sovrapubic subcutaneous tissue.
We have observed in all patients a subjective reduction of penile deviation, a reduction of penetration discomfort and an improvement of quality of erections. In four patients  we have obtained the reduction of dimensions of plaques.
CO2 could be considered a powerful antioxidant against endothelian dysfunction and oxydative stress with easy management and poor toxicity.
In conclusion, CO2, as natural antioxidant  could reduce the activity of inflammatory agents as NF-kB protein, involved in the evolution of PD.

Discussion

The tunica albuginea is a thick fibroelastic sheath composed predominantly of thick collagenous bundles and elastic fibers surrounding the trabecular smooth muscle of the corpora cavernosa. Any defect in tunica albuginea can deform penile fibroelastic framework, resulting in curvature or bend, shortness, progressive lack of elasticity, and also occasionally affecting hemodynamic function of the penis.(1,2)
The inflammatory process origin is unknown. it is postulated the occurrence of penile trauma.
Injury causes delamination of the tunica albuginea predominantly at the dorsal, midline septum resulting in small hematoma.(3,4)
Inflammation, induration, and accumulation of leukocytes increase ROS activities with a chain of biochemical events leading to fibroblast proliferation and resulting in collagen and fibrin biosynthesis-deposition between the layers of the tunica albuginea (6)
It seems to be involved some specific inflammatory proteins that provoke the rising of radicals of oxygen and Nitric oxide. The principal protein involved in the genesis of ROS is NF-kB.
The nuclear transcription factor NF-kB is a heterodimeric, sequence-specific transcription factor found in many cells. In unstimulated cells, NF-kB is found in the cytoplasm and is bound to its inhibitor kB, which prevent it from entering nuclei. A number of stimuli have been shown to activate NF-kB, including cytokines, activators of protein kinase C, viruses and oxidants. (5)
In PD altered CO2 levels could impact upon disease progression. CO2 levels can be sensed by cells resulting in the initiation of physiologic and pathophysiologic responses. A role for CO2 in the regulation of gene transcription has recently been identificated with exposure of cells and model organisms to high CO2 leading to suppression of genes involved in the regulation of innate immunity and inflammation.
Recent evidence suggests that CO2 may also directly regulate gene expression through the NF-kB pathway. The suppression of NF-κB activity by hypercapnia was recently provided by the demonstration of CO2-induced nuclear localization of the IKKα subunit.(5)
Therapeutic hypercapnia seems to have a suppressive effect on NF-κB signaling.(5)
Carboxytherapy leads to flood vassels dilatation in the area where the gas is injected. This reaction to carbon dioxide injection gives a better oxygenation of skin layers with increased lipolysis capabilities. Carboxytherapy has been used for over 70 years in Europe where it was discovered (France, Royat). The procedure was widely used to treat ischemic vascular diseases because of the vasodilation properties of CO2. The most common co2 treatments are: cellulite reduction, liposuction complementary solution, arterial diseases associated with diabetes and skin ulcers (7)
Carboxytherapy stimulates microcirculation at the level of metarterioles, arterioles and precapillary sphincteres by increasing tissue flow velocity and consequently, by improving lymphatic drainage.(7,8)
In PD the use of carboxytherapy shows in all patients subjective improvement of erection and in 4 cases the reduction of plaque dimensions with a very easy management and free risk subministration.Side effects are minimal and resolve quickly, and include mild pain at the injection site and possible self limiting bruising of the tissues.
Preliminary qualitative and quantitative results could encourage an extended experimentation of carboxytherapy in PD conservative treatment

References

1 Gelbard MK, Dorey F, James K. The natural history of Peyronie’s disease. J Urol 1990; 144: 1376 – 1380.
2 Hellstrom WJG, Bivalacqua T. Peyronie’s disease: etiology, medical and surgical therapy — Review. J Andrology 2000; 21: 347 – 354.
3 Devine CJ, Somers KD, Ladaga LE. Peyronie’s disease: pathophysiology. Prog Clin Biol Clin Biol Res 1991; 370: 355 – 358.
4 Somers KD, Sismour EN, Wright GL. Isolation and characterization of collagen in Peyronie’s disease. J Urol 1989; 141: 629 – 635.
5 Taylor C, Cummins E Regulation of gene expression by carbon dioxide Physiol. 2011 February 15; 589(Pt 4): 797–803.
6 Schwarzer U, Klotz T, Braun M, et al.: Prevalence of Peyronie’s disease—results of an 8,000 men survey. J Urol 2000, 163 (suppl):A742.
7 Parassoni L,Varlaro V. la carbossiterapia: una metodica in evoluzione. Riv La Medicina Estetica, anno 21, n.1, gennaio-marzo 1997. Editrice Salus Internazionale, Roma.
8 Parassoni L,Albergati F,Varlaro V, Curri SB. La carbossiterapia in tema di meccanismi d’azione. Riv. La Medicina Estetica, anni 21, n.1, gennaio-marzo 1997. Editrice Salus Internazionale, Roma.

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