The goal of this randomized interventional clinical trial is to learn if placement of a thin layer of fatty tissue (fat graft) beneath a split-thickness skin graft on the surface of the penis improved outcomes of surgery in men who are scheduled to undergo reconstructive surgery on their penis and genitals. This is a randomized study, meaning that half of participants will receive the fat graft with their standard-of-care surgery, and half will have their standard-of-care surgery alone. Fat grafting underneath split-thickness skin grafts in other parts of the body has been shown to improve healing of the skin graft. Both study groups will be followed for specific outcomes through outpatient clinic visits for the first 12 months after their surgery, as well as chart review. Questions the investigators hope to answer include: * Does fat grafting improve the pliability and feel of the penile skin after grafting * Does fat grafting change the penile length after surgery * Does fat grafting improve sexual function, urinary function, and genital self-image after surgery * Are there any unforeseen complications related to the fat grafting procedure Participants will be asked to complete questionnaires related to sexual, urinary, and genital self-image questionnaires before surgery, 3 months after surgery, and 12 months after surgery. Noninvasive testing of the penile skin will also be performed at participants' routine appointments.
The investigators seek to study a novel adipose-based therapeutic strategy to improve cosmetic and function outcomes at the time of penile split-thickness skin graft (STSG) application during penile reconstruction. This entails a therapeutic repurposing of commonly utilized fat and skin grafting protocols to provide a fat-first reconstruction to address each of these limitations in one simple, economical, and widely accessible treatment for point-of-care penile reconstruction. Autologous adipose tissue is ideal as an adjunct to penile split-thickness skin grafting because it: 1) provides immediate, biologic soft tissue coverage with minimal to no donor site burden; 2) remains viable in poorly vascularized wound beds and can be placed as a biologic dressing without specialized microsurgical care; 3) enhances angiogenesis to mitigate risk of infection of deeper structures; 4) mitigates adhesions to underlying structures; and 5) can be used as immediate platform for rapid restoration of cutaneous integrity. By leveraging these techniques, the investigators seek to provide a safe, effective, and available option to augment standard-of-care reconstruction techniques. Multiple conditions can lead to a need for penile reconstruction. Penile trauma, including burns, penetrating injury, blast injury, and friction injury can irreversibly damage penile skin, leading to a need to resurface the shaft and/or glans of the penis with local tissue flaps or autologous grafts. Infectious processes, most notably Fournier's gangrene, can also lead to loss of penile skin. Finally, adult-acquired buried penis (AABP) disease, a condition wherein the penis becomes trapped by adjacent soft tissues leading to chronic inflammation and loss of penile epithelial integrity, can require surgical excision of penile skin as part of a multicomponent repair. In all of these cases, STSG of the penile shaft is considered standard of care if local flaps, such as scrotal flaps, are not available for reconstruction due to overlapping disease processes. STSGs are commonly utilized to allow for rapid, definitive closure and restoration of the integument. While STSG graft take on the penis following these processes is successful \>95% of the time with restoration of urinary outcomes, patients who have undergone the procedure typically report dissatisfaction with the cosmetic appearance of their penile skin. This is due to adhesion of the STSG to the fixed Buck's deep fascia of the penis, which occurs due to the loss of the mobile Dartos fascia during the time of initial insult/injury. The combination of adhesion and graft contracture/fibrosis can lead to a "plasticky" feeling of the penile skin, which is especially bothersome given the expansile nature of the deep cavernosal bodies during sexual arousal. While current sexual outcomes in patients undergoing penile reconstruction are superior to patients who do not undergo reconstruction, there exists significant room for improvement. There currently exist no off-the-shelf products with proven efficacy in improving outcomes. Adipose tissue is a prime candidate for this application due to its autologous origin, ease of procurement with minimal-to-no additional donor site morbidity, and abundant availability in patients, alongside its unique reconstructive and regenerative capacities. The use of autologous adipose in delayed tissue reconstruction is well established. However, the full therapeutic potential of adipose tissue remains underexploited. Fat grafting provides immediate soft tissue bulk, enhances angiogenesis, is both immunomodulatory and enhances immunologic homing, and supplies mesenchymal cells for soft tissue healing. Fat grafting is viable in hostile recipient beds including infected/contaminated and poorly vascularized wounds such as the diabetic foot ulcer, irradiated skin, and burn scars. Grafting of autologous fat tissue is a minimally invasive surgical technique that starts with the harvest of small particles (2-5 mm) of fat tissue from the abdomen or using liposuction. Sometimes, fat graft can be harvested from tissue that is removed for other reasons. This technique utilizes incisions smaller than 5 mm in length and rapid intraoperative processing allowing for immediate transplantation of a patient's own tissue in a single operative procedure. Autologous fat can also be obtained from adipose tissue removed intraoperatively, which is a standard component to AABP repair, and processed intraoperatively for immediate use. This follows a standard fat grafting preparation protocol currently being used for standard of care cases. A multitude of data exist to support the utility of autologous fat grafting for other disease processes at a variety of anatomic sites. Applications that have been subject to rigorous prior study include: * Improvement in soft tissue volume, pliability, and skin quality after autologous fat grafting of atrophic amputation stumps * Improvement in tissue pliability in a porcine burn model * Improvement in human burn patients when autologous fat grafting was performed beneath a STSG overlying tendon in a burn patient In the study described herein, participants will undergo the standard-of-care baseline reconstructive surgery for their primary disease process. This will include any necessary debridement, penile degloving, and soft tissue excision of the penis, genitals, and surrounding tissues as indicated by their primary traumatic, infectious, or other disease process. Post-operative wound care will proceed along standard-of-care pathways and will not be altered for the purposes of this protocol. It is important to recognize that no cell extraction or isolation will be performed in this trial. The fat graft is regulated as a standard surgical procedure with no more than minimal manipulation of the fat tissue. Fat graft injection has been widely adopted by plastic surgeons, dermatologists, and ophthalmologists in clinical practice. Because these are autologous fat grafts that undergo minimal manipulation, they are regulated as a standard surgical procedure and are well-tolerated by patients with minimal safety risks. Only simple processing will be performed with the fat tissue to improve its texture and compliance as is already the standard of care and commonly performed. As autologous fat grafting is well known to soften scarring from trauma, surgical manipulation/incisions, and radiation fibrosis, the investigators believe this approach will be efficacious and well-tolerated due to the common anatomic factors seen in the penis and other parts of the body.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
24
In this intervention, subjects will undergo their standard-of-care reconstructive urologic surgery with penile split-thickness skin grafting as medically indicated for treatment of their underline penile/genitourinary condition(s). In addition to this reconstruction, autologous fat grafting will be performed beneath their penile skin graft. For subjects from whom a sufficient quantity of healthy adipose tissue is excised as part of the standard-of-care reconstructive surgery they have elected to undergo, the autologous fat graft will be processed from this specimen and placed between the skin graft and fascia of the penis. For subjects from whom a sufficient quantity of healthy adipose tissue is not excised as part of their standard-of-care reconstructive surgery, lipoaspiration (liposuction) will be performed to harvest fatty tissue that will subsequently undergo minimal processing for grafting.
Subject eligibility for this study is contingent upon a baseline disease process in which subjects require and are appropriate for genitourinary reconstruction with penile split-thickness skin grafting as their surgical standard of care. Patients in both arms will receive the standard of care reconstruction and split-thickness skin grafting. The donor site for the split-thickness skin graft with be at the discretion of the operating surgeon during the case and will not be affected by enrollment and/or allocation within the trial.
UPMC Mercy Hospital
Pittsburgh, Pennsylvania, United States
Penile Tissue Pliability
The primary outcome of this study will be cutometric assessment of penile tissue pliability following split-thickness skin grafting. This will be measured using established noninvasive, nondestructive techniques that are not expected to cause significant discomfort or distress to patients. The numeric outcome of this, as measured in millimeters, will be directly compared between the experimental and active comparator arms. More pliability is manifested as increased pliability, as measured in millimeters.
Time frame: 3 and 12 months postoperatively
Sexual Function
Subjects' postoperative sexual satisfaction and sexual function will be assessed using the 15-question validated International Index of Erectile Function questionnaire. Pre- and post-operative total scores (measured on a scale of 0 to 45, where a higher score indicates better sexual satisfaction/function) will be compared in a pairwise manner between arms of the study to determine if autologous fat grafting confers increase improvement on IIEF relative to the active comparator arm.
Time frame: Preoperatively, 3 months postoperatively, and 12 months postoperatively
Urinary Function
The Internatonal Prostate Symptom Score (IPSS) validated patient questionnaire will be utilized to assess subjects' satisfaction with their urinary function. This questionnaire includes seven Likert-style questions assessing seven domains of urinary function, where a composite score of 0 represents no symptoms and a composite score of 35 represents maximum symptom burden. The questionnaire also contains one additional quality-of-life question, in which 0 represents maximum aggregate satisfaction with urinary function and 6 represents the worst possible satisfaction with urinary function. The pre- and post-operative scores will be analyzed in a pairwise manner, and the change in scores will be assess between the experimental and active comparator groups.
Time frame: Preoperatively, 3 months postoperatively, and 12 months postoperatively
Genital Self-Image
Subjects' pre- and post-operative subjective genital self-image will be assessed using the 7-question validated Male Genital Self-Image Scale (MGSIS) questionnaire. Pre- and post-operative total scores (measured on a scale of 7 to 28, where a higher score represents a more positive self-image) will be compared in a pairwise manner between arms of the study to determine if autologous fat grafting confers increase improvement on MGSIS relative to the active comparator arm.
Time frame: Preoperatively, 3 months postoperatively, 12 months postoperatively
Safety and Surgical Complications
Patient safety and surgical complications will be closely monitored throughout the convalescence period of the study in the standard manner for their genitourinary reconstruction procedure. Patients will be seen in-person, and contacted via telephone, for assessment of their wounds. At these visits, interval information will be collected to monitor for adverse events, such as graft failure, infection, incisional dehiscence, graft donor site hematoma, and other wound complications. All adverse events will be scored using the Clavien-Dindo classification system, and classified as minor (Clavien-Dindo 1-2) and major (Clavien-Dindo 3-5). The frequency of major and minor complications in the experimental arm will be compared to the frequency in the active comparator arm.
Time frame: Immediately postoperatively through 12 months, including in-person visits at 7 days, 4 weeks, 3 months, and 12 months postoperatively. A telephone call will also be initiated 6 months postoperatively.
Stretched Penile Length
Stretched penile length and associated tissue mobility will be measured and recorded. Average stretched postoperative penile length in the experimental group, as measured in centimeters, will be measured relative to that in the active comparator arm.
Time frame: Intraoperatively, 3 months postoperatively, 12 months postoperatively
Penile Pain and Sensitivity to Monofilament Testing
Penile pain and sensitivity assessment will be performed using standardized protocols for grafting on other areas of the body. These noninvasive methods provide a subjective readout of pain and sensitivity. Specifically, the Semmes Weinstein monofilament test will be used to identify the pressure threshold at which perceptible sensation can be elicited with closed eyes. This is scored on a scale of 1.65-6.65 based on the monofilament sizes within the standard kit. Patients with lower numbers, indicating a smaller monofilament/less pressure can elicit a perceptible response, have greater sensitivity than those with higher numbers. If pain is elicited, they will also be assigned a score on the scale listed above, with a lower score suggestive of lower pain threshold. This will be assessed on the right lateral aspect of the penis, left lateral aspect of the penis, and glans.
Time frame: 3 and 12 months postoperatively
Penile Sensitivity to Two-Point Discrimination Testing
The sensitivity of the grafted penile skin will be assessed using the static two-point discrimination test, which is a commonly used test for skin sensitivity testing. In this test, a pair of calipers will be used to determine the spacing at which the patient can detect two discrete points of pressure, as measured in millimeters. A larger distance suggests less sensitivity, while a shorter distance suggests more sensitivity. This will be assessed on the right lateral aspect of the penis, left lateral aspect of the penis, and glans.
Time frame: 3 and 12 months postoperatively
Penile Graft Elasticity
Penile graft elasticity will be assessed using noninvasive skin tensiometry. The outcome of this, as measured in mm, will be compared between the experimental and active comparator groups.
Time frame: 3 and 12 months postoperatively
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