Post-Mohs Surgical Wounds Treated With Intact Fish Skin Graft: A Multicenter Analysis

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Surgical wounds, such as post-MMS (ie, post-Mohs) wounds, present an opportunity for evaluation of different wound treatments. For patients with nonmelanoma skin cancers, MMS may be considered the treatment of choice.¹ It is recommended for high-risk basal cell carcinoma and cutaneous squamous cell carcinoma.² Treatments for post-Mohs surgical wounds vary and include the use of full- and split-thickness skin grafts,³ as well as flaps, primary closure, amniotic membrane,⁴ and collagen-glycosaminoglycan silicone bilayer matrices.⁵ 

IFSG is composed of a single component—minimally processed, decellularized material from the skin of Atlantic cod (Gadus morhua), which is sustainably fished in the Arctic waters around Iceland. Cod skin displays gross structural similarity to human dermis. The fish skin is descaled, decellularized, lyophilized, and sterilized prior to use. One prospective randomized controlled trial compared IFSG with porcine xenograft,⁶ and another compared IFSG with human amnion/chorion membrane in punch biopsy wounds.⁷ Both studies demonstrated a faster rate of wound closure with IFSG than with the comparator.^6,7 There are numerous anecdotal experiences of the use of IFSG in a range of wounds, but in 2023 an industry-sponsored (Kerecis LLC) registry was initiated to provide a prospective method of collecting and assessing the utility of IFSG in a wide variety of wound types. This study represents the first publication from that registry since the prospective registry was built. 

This is the first non-interventional, multicenter series to examine the real-world experience of using an IFSG on post-Mohs surgical wounds. The goal of Mohs surgery is to excise skin cancer by meticulous intraoperative examination of complete margins, and the technique is associated with an exceptionally high cure rate. Once the skin cancer is resected and the surgical margins are clear, the Mohs surgeon is then faced with a decision concerning the best way to reconstruct the defect. Several factors may influence the decision, including anatomic location, size and depth of the defect, patient age, patient history, quality of surrounding tissue, and health of the host, as well as any specific cosmetic needs of the patient. Traditional reconstruction would include surgical options such as primary tissue rearrangement, full- or split-thickness grafts, or flaps.⁸ Nonsurgical options such as secondary intention could involve a lengthy healing process and extensive wound care. Depending on anatomic location, the wound may be painful and inflamed.

Results from participating US facilities with post-MMS IFSG patients enrolled in the registry titled “Prospective observational registry of safety and effectiveness of acellular fish skin grafts in treatment of cutaneous wounds” are presented. This open-label, prospective registry was created to study the real-world safety and performance of a fish skin acellular dermal matrix on various types of wounds (ClinicalTrials.gov identifier: NCT05898698). Data collection was ongoing as of April 17, 2024, when data were retrieved for this interim assessment; this trial has subsequently been closed and moved to a different registry (ClinicalTrials.gov identifier: NCT06384183).

This is an interim report on an open-label, prospective registry studying the real-world safety and performance of an IFSG on various types of wounds. This non-interventional observational registry collects data over 32 weeks after patient enrollment. The primary objective is to collect real-world information on the time to and frequency of complete wound closure by or at 32 weeks. The secondary objective is to determine the average median number of IFSG applications used to achieve wound closure. 

Any participant age 18 years or older who was identified by the investigator to meet the inclusion and exclusion criteria was eligible for the registry. It is planned to enroll up to 200 participants at sites within the United States. Potential participants were informed of the registry by investigators or research staff (R.O., C.A., D.S.). Participants who agreed to participate and who met the inclusion and exclusion criteria were enrolled in the registry. 

Registry plan

Participants who received either MariGen or Shield devices (both IFSGs; Kerecis Limited) were included in the study, and weekly data collection continued for 32 weeks. Participants received standard of care wound treatment in addition to IFSG as determined by their investigator. The first patient was enrolled on June 22, 2023. 

Patients

Review and approval from WCG IRB, formerly Western Institutional Review Board, was received and maintained during data collection (IRB#00000533). Any patient undergoing placement of IFSG on a superficial wound at a participating site could be entered in the registry. It is important to note that it was not mandatory that all patients receiving IFSG at a site be enrolled, which allowed for selection bias. The registry complies with International Council for Harmonisation guidelines for good clinical practice and applicable US federal regulations. Each participant provided written or verbal informed consent according to WCG IRB requirements, which was documented at the investigative site. One target wound per patient was identified by the investigator as appropriate for using IFSG. 

Data collection

Investigative sites were responsible for reviewing the medical record and recording data for the registry into standard electronic case report forms. An electronic data capture system (Greenlight Guru Clinical, formerly SMART-TRIAL; Greenlight Guru) was used, which permitted both data entry at investigative sites and quality checks by the sponsor. Periodic data review and cleaning was performed by sponsor personnel, including the issuing of data queries to investigative sites as needed. The data were retrieved on April 17, 2024, for an interim assessment.

Statistical analysis

The interim assessment was performed with the understanding that enrollment and data collection remain ongoing. Because of the observational, open-label registry design, there was no treatment randomization. Continuous data were summarized using descriptive statistics, and categories are described using frequencies and percentages. All analysis was performed using Python 3.11.7 (Python Software Foundation).

To assess the primary objective within a real-world clinical setting, the date of complete wound closure, as reported by the investigative sites, was used as the primary end point. The secondary end point was evaluated by analyzing the available wound measurements and number of IFSG applications; in addition, any hospital readmissions for index wound-related event(s) were recorded. Kaplan-Meier survival analysis was used to estimate the time to complete wound closure across the registry. This nonparametric method allowed the authors of the present study to account for censored cases, thereby providing a more accurate depiction of wound closure dynamics over the study period.

The analytical approach encompassed an appropriate range of descriptive statistics and frequency distributions to comprehensively describe the treatment patterns and outcomes observed. Kaplan-Meier survival analysis was used to assess the time to wound closure, and these data were used to estimate the median time to wound closure and to visualize the probability of wound closure over the current registry period. A Cox proportional hazards model was used to identify potential factors influencing wound closure rates. This allowed examination of the relative effect of variables such as sex, cardiovascular disease, and hypertension on wound closure, providing further insight into treatment dynamics.

Each participant had a wound that was treated with IFSG as part of their Mohs surgical care. As of April 17, 2024, there were a total of 41 participants enrolled in the registry who had undergone post-Mohs surgery. For all patients, IFSG was placed at the time of Mohs surgery. 

The post-Mohs participants’ mean (SD) age was 77.6 (8.9) years (range, 53–101 years), with females comprising 24% of participants (n = 10). In terms of race and ethnicity, most patients self-identified as White (95% [n = 39]), with a smaller percentage (5% [n = 2]) identifying as Hispanic, which differs from the overall US population⁹ but is consistent with the population with skin cancer.¹⁰ The mean (SD) body mass index was 26.8 (4.3), with a range from 19.7 to 41.1, indicating a diverse spread in body composition among the participants. Relevant participant demographics and medical history are presented in Tables 1 and 2, respectively.

The 41 target wounds were located in the head and neck (n = 26), chest and thorax (n = 1), upper extremities (n = 5), and lower extremities (n = 9). The average wound surface area was 7.58 cm² (median, 4.00 cm²). When stratifying the wounds by upper body vs lower extremity location, it was found that 32 patients had wounds located on the upper body and 9 had wounds on the lower extremities. Lower extremity wounds exhibited a higher average surface area than upper body wounds (8.52 cm² [median, 5.20 cm²] and 7.31 cm² [median, 3.05 cm²], respectively). 

The primary end point focused on wound closure. Over the course of the registry for patients with post-Mohs surgery, 40 of 41 wounds achieved complete wound closure (97.6%), and 1 patient was lost to follow-up (2.4%). The median time to wound closure for the entire cohort, as determined by Kaplan-Meier analysis, was 5 weeks. For head and neck wounds specifically, the Kaplan-Meier median time to wound closure was 4 weeks. This statistic represents the duration at which half of the wounds had successfully closed, providing a measure of the central tendency of wound closure time within the study population. The identification of a 5-week median wound closure time supports the efficacy of the IFSG used within the registry. Figure 1 illustrates the Kaplan-Meier time to wound closure. The median time to healing was 4 weeks for wounds located on the upper body and 5 weeks for those on the lower extremities.

In this small cohort, sex, cardiovascular health, hypertension, and diabetes had no statistically significant effect on wound closure rates or time to closure. Figure 2 demonstrates the progression of wound closure in 2 patients.

The median number of IFSG applications used was 2 (mean, 1.82). Kaplan-Meier analysis showed a median time to wound closure of 4 weeks for those achieving complete closure. The timing of the application provides insight into the real-world usage of IFSG in the treatment of Mohs wounds, which may affect the speed of wound closure.

Between June 2023 and April 17, 2024, 5 adverse events were reported, of which 3 were reported as “serious” per the investigative site. The 3 events occurred in 3 different patients (Table 3). According to the investigators, none of the events were related to IFSG.

This interim registry study explored the efficacy of IFSG in promoting wound closure, focusing on the time to complete wound closure and secondary outcomes such as frequency of treatment application. The findings presented herein provide insights into wound management and treatment dynamics in a real-world clinical setting.

Kaplan-Meier analysis indicated a median time to wound closure of 5 weeks among all patients, and a median of 4 weeks for head and neck wounds, highlighting the potential of IFSG to facilitate relatively rapid wound closure. A previous prospective Mohs study reported mean time to closure of 6.5 weeks in the 40 patients in the control arm whose wounds were healed by traditional secondary intention.¹¹ There was a larger distribution of wounds in the head and neck than in the rest of the body, making the evidence more supportive of therapy in the supraclavicular area than in the rest of the body. 

In the present study, 97.6% of patients achieved complete wound closure. Of those, the Kaplan-Meier median number of visits per patient was 5 (mean, 4.68), reflecting a consistent treatment regimen that facilitated effective monitoring and intervention. Among the patients who achieved wound closure, the median number of IFSG applications used per patient was 2 (mean, 1.82). This shows that IFSG was often sufficient as a primary treatment, with only a subset of patients requiring additional IFSG applications due to wound complexity or comorbidities, at the physician’s discretion. 

Real-world registry data are not without some limitations. The study data presented are part of an interim analysis, with continuing patient enrollment and ongoing data entry and monitoring as of the time the reported data were retrieved. Incomplete data result from inconsistent completion of medical records, and thus, affect the available data for analysis. Consequently, the analysis of secondary outcomes was limited to those for which sufficient and reliable data were available, primarily wound area measurements and the number of IFSG applications. Information on secondary dressings or the frequency of dressing changes was not part of the registry data collection. Additionally, missing data from patients who were lost to follow-up may affect the longitudinal data, adding potential bias to the data of those patients with complete data sets. 

The relatively small sample size of 41 patients may limit the statistical power of this interim analysis. This small sample size provides insights into the use of IFSG in this area. Further studies with larger sample sizes that are sufficiently powered should assist with providing stronger determination about the efficacy of IFSG and wound closure. The diversity profile of patients presented in this report is limited, which restricts the generalizability of the data to patients who are not White, although the majority of Mohs surgery is performed in White patients. 

Data consistency and quality in the primary medical record and subsequent transcription into the study database may result in data entry errors and misinterpretation of the data, thus affecting the quality and reliability of the study findings. Participant selection in the registry may also limit the generalizability of the study findings, as may the fact that this cohort was derived from only 2 high-volume centers.

Whereas the ongoing registry highlights a potential role for IFSG in accelerating wound closure, it does not necessarily answer the question of proportion of wounds closed; that will require a treatment arm. The ongoing collection of data promises to enhance understanding of the factors that influence wound closure dynamics, potentially leading to targeted interventions that optimize treatment strategies and improve patient care outcomes. The results presented provide the Mohs surgeon with viable options to consider in the complex reconstruction paradigm for skin cancer. Registry data show that with only 1 to 2 applications, the post-Mohs wounds closed quickly with minimal complications and required minimal wound care. This registry remains a critical tool for evaluating real-world efficacy and informing future therapeutic directions in wound management.