Tolerability and Efficacy of Newly Developed Penile Injection of Cross-linked Dextran and Polymethylmethacrylate Mixture on Penile Enhancement

6 Months Follow-Up

D Y Yang; W K Lee; S C Kim

Disclosures

Int J Impot Res. 2013;25(3):99-103. 

In This Article

Discussion

Many different types of penile enhancement surgery are performed all over the world, although there are medicolegal issues and paucity of scientific data.[2] Currently, as the need for safer, effective and less-invasive procedures are increasing, penile enhancement procedures using injectable products are in high demand. Injectable soft-tissue substitutes provide an affordable, nonsurgical alternative for correcting contour defects and soft-tissue augmentation. Several penile injection materials have been used for penile enhancement, including autologous fat, silicone, collagen and hyaluronic acid (HA).[6,8–11]

The injection of autologous fat was initially thought to be a promising technique. However, during the injection process, a significant number of adipocytes are ruptured or reabsorbed, and probably the final result leaves only 10% of the fat cells intact.[12] Results for autologous fat injections are considered unpredictable, because of the lack of adequate blood supply to the injected fat and because the plane into which the adipocytes are injected has not been determined.[11] Small amount (up to 0.75 ml) of silicone injection has been commonly used for cosmetic purposes, with satisfactory results and relative safety, mainly in cases of soft-tissue augmentation and restoration of damaged skin. However, in order to achieve penile enhancement, larger volumes of silicone, ranging from 100–150 ml, are required. Therefore, the silicone injection has not been recommended, because of the development of severe complications. Some of the complications were related to the large volumes injected, and others were due to drifting and distant migration, swelling, penile distortion and idiosyncratic and late granulomatous reactions.[2,13] In addition, injection of silicone into the penis increases the likelihood of damaging blood vessels and nerves, thereby causing loss of sensation and erectile dysfunction.[14,15] The collagen products were the first injectable fillers used for esthetic improvement, because endogenous collagen functions as the structural base for the skin, providing strength and support.[6] However, the collagen caused rapid degradation, required frequent reinjection and produced infrequent but significant hypersensitivity reactions.[16]

Unlike the aforementioned products, cross-linked dextran and PMMA mixture was well-tolerated, did not cause serious adverse events and provided a significant penile enhancement in this study. All of 19 subjects (100%) fulfilled the criteria for primary end point of penile girth enhancement. Interestingly, 16 of 19 subjects (84.2%) fulfilled the criteria for primary end point of penile length enhancement, and the mean increase of flaccid penile length after 6 months was 2.3±1.4 cm (63.2%). There are only few studies showing an increase in penile length after penile injection using any materials One of the hypotheses is the splint effect of cross-linked dextran and PMMA mixture. As the mixture of cross-linked dextran and PMMA is evenly distributed between Buck's fascia and dartos fascia, it prevents the physiologic contraction of the penis and leads to the lengthening effect. From the viewpoint of adverse events, cross-linked dextran and PMMA mixture was superior to the aforementioned products. There were only a few mild adverse reactions, possibly caused by technical mistakes during injection, rather than drug-induced side effects.

Lipen-10, cross-linked dextran and PMMA mixture, is newly developed dermal filler for soft-tissue augmentation, and is a commercially available product approved by the Korean Food and Drug Administration in 2010. PMMA-based dermal filler was approved in USA in 2006 for the treatment of nasolabial folds.[5]

Once injected, the smooth, electrically uncharged PMMA microspheres are encapsulated by endogenously derived connective tissue, preventing migration of the microspheres. The PMMA microspheres resist phagocytosis and are not degraded by enzymatic digestion.[6] Histological studies indicate that each microsphere is encapsulated by a thin layer of collagen, macrophages and fibroblasts by as early as 1 month.[17] Cross-linked dextran, the other component of mixture, is derived from dextran used as a volume expander, and consists of microspheres similar to PMMA. The positive surface charges of dextran apparently attract macrophages. In turn, the macrophages release TGF-β and interleukins, which stimulate fibroblasts to produce collagen fibers. After being extensively reabsorbed, dextran is replaced by the body's own tissue.[7]

Jang et al.[18] studied both the bio-safety and the volume-related effect of Lipen-10, as soft tissue filler in the rat model for 13 weeks. During the experimental period, there were no dead rats and scratching behavior which is a most common symptom when rejecting foreign body was observed. The volume of injected mixture was maintained sufficiently. Complete blood count finding indicated that there were no significant differences in the number of inflammatory cells between control and experimental group. In addition, the parameters of hepatic toxicity (aspartate aminotransferase, alanine transaminase, alkaline phosphatase, γ-glutamyl transpeptidase, lactate dehydrogenase), renal toxicity (creatinine, blood urea nitrogen, cholesterol, albumin, phosphorus), and other organ toxicity (calcium, triglyceride, and creatine phosphokinase) using serum biochemical analysis did not show the significant differences between the control and experimental group, suggesting that systemic toxicity was not found. Histopathological findings indicated that the subcutaneous tissue had red color microsphere which capsulated by collagen near the injection site. Furthermore, the infiltration of inflammatory cells was not observed in the injected sites of all experimental groups. They concluded the Lipen-10 could be a safe substance for soft-tissue augmentation maintaining tissue volume. Our prospective study was designed based on their results.

Among the different kinds of PMMA-based dermal fillers, Artefill (Artes Medical, San Diego, CA, USA) consisting of PMMA microspheres with 3.5% bovine collagen and 0.3% lidocaine, is well-known and widely used.[5] The safety and effect of this filler was approved in USA in 2006,[5] although there is no study on penile enhancement. However, one of the major drawbacks is its potential for hypersensitivity reactions, because of the presence of bovine collagen. Artefill requires that all subjects undergo appropriate skin testing several weeks in advance of their planned procedure.[5,19,20] Unlike Artefill, the injection mixture used in this study contained cross-linked dextran instead of bovine collagen. Dextran is widely used in the treatment of vesicoureteral reflux, is safe enough to be recommended in children, and allergy test is not needed.[21]

HA-based dermal filler is widely used for penile enhancement. From both biocompatibility and immune viewpoints, as HAs are naturally occurring hygroscopic polysaccharides found in the extracellular matrix, they seem to be an ideal filling substance for soft-tissue augmentation.[22] However, the duration of effect for HA-based dermal fillers as a group ranges from 3–12 months, making this class of temporary fillers intermediate in duration of effect, whereas PMMA-bssed dermal fillers are regarded as permanent or semi-permanent fillers.[6] Recently, Lim et al.[23] studied PMMA- and HA-based filler as an injection laryngoplasty material in canine model for 9 months. They reported that both PMMA and HA were safe and relatively durable as fillers for the vocal folds. They also reported that up to 30% of the HA was gradually reabsorbed over time, while the dimension of the augmented region after 9 months was similar to that achieved in the PMMA group after only 1 month. More recently, Jang et al.[18] studied the volume effect of cross-linked dextran and PMMA mixture (Lipen-10) in the rat model, compared with HA-based dermal filler. At 13 weeks after injection, although the volume of the HA-based filler was significantly decreased, the volume of cross-linked dextran and PMMA mixture was maintained sufficiently.

There were a few limitations to this study. First, the duration of follow-up was not enough to confirm the long-term effect of cross-linked dextran and PMMA mixture. A longer term follow-up over a year is needed for the clinical use. Also, there was no control group in this study. Lastly, evaluation of patient satisfaction and partner's response should be followed.

In conclusion, penile injection of cross-linked dextran and PMMA mixture showed a significant enhancement of penile girth, good durability at 6 months post-treatment, and was well-tolerated, without serious adverse events. Penile injection of cross-linked dextran and PMMA mixture may be a new effective tool for penile enhancement. Long-term follow-up for tolerability and efficacy should be needed to confirm its value in penile enhancement.

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