Is there a role for platelet rich plasma injection in vulvar lichen sclerosus? A self-controlled pilot study.

BACKGROUND: Owing to the evidence that as many as 30-40% of patients with vulvar lichen sclerosus (VLS) fail to report a remission of symptoms with first-line corticosteroid treatment (TCS), especially as what regards dyspareunia, we aimed to analyze patients' satisfaction following vulvar injection of autologous platelet-rich plasma (PRP). This is intended as an adjunctive treatment, to be used following TCS, and appears to promote tissue repair. It may also possibly have immunomodulatory proprieties. MATERIALS AND METHODS: Patients with VLS were considered eligible for this pilot study if, despite having been treated with a 3-month TCS regimen, they reported a persistence of symptoms. PRP was produced in a referral center using a manual method and a standardized protocol. Each patient received three treatments 4 to 6 weeks apart. RESULTS: A total of 50 patients with a median age of 53 years [IQR 38-59 years] were included in the study. 6 months after the last injection of PRP all patients were either satisfied or very satisfied with the treatment (100%; 95% CI 93-100%). Median NRS scores for itching, burning, dyspareunia and dysuria were significantly reduced (p < 0.05) and FSFI, HADS and SF-12 questionnaires revealed a significant improvement in sexual function, psychological wellbeing and quality of life (p < 0.05). The number of patients reporting the need for maintenance TCS treatment was reduced by 42% (p < 0.001) and an improvement in vulvar elasticity and color was reported in all patients. CONCLUSION: Following standard medical therapy, PRP may be effective not only in improving symptoms, but also in restoring function.

Fat Grafting in Vulvar Lichen Sclerosus: Long Term Follow-Up.

OBJECTIVE: The rationale for the use of autologous fat grafting in the treatment of vulvar lichen sclerosus (VLS) consists in reduction of inflammation, regeneration of tissues, volume increase, and pain fiber control. The main outcome of this study was the evaluation of patients' satisfaction after treatment. Secondary outcomes included modifications in symptoms, psychosexual wellbeing, vulvar hydration, and histology after surgery. METHODS: Eligible for this study were women aged 18-85 years with a histological diagnosis of VLS who underwent at least one autologous vulvar fat grafting at the authors' center, between 2010 and 2019. In 2021, all women underwent a clinical reevaluation, comprehensive of vulvoscopy, vulvar biopsy, and handing out of validated questionnaires. RESULTS: Overall, 88.7% of patients declared themselves very satisfied/satisfied with the procedure. All symptoms were improved postsurgery; in particular, the difference was statistically significant for pruritus, burning, and dyspareunia ( p < .05). Sexual function was also improved at time of reevaluation, as were depressive and anxiety symptoms ( p < .05). No cases of vulvar intraepithelial neoplasia or cancer occurred during follow-up and vulvar architecture remained stable, although patients reported a significantly reduced need for topical steroids ( p < .0001). Lastly, in postoperative biopsies, inflammatory infiltrate was stable or reduced, and the distribution of elastic fibers was comparable or restored in most patients. CONCLUSIONS: Patient satisfaction with fat grafting is detectable up to 11 years after surgery, and as such, it may represent a valid therapeutic option in selected cases of VLS.

High-Quality Lipoaspirate Following 1470-nm Radial Emitting Laser-Assisted Liposuction.

BACKGROUND: Laser-assisted liposuction (LAL) has been used to maximize viable adipocyte yields in lipoaspirates, although optimizing tissue processing methods is still a challenge. A high-quality lipoaspirate has been a key factor for extended graft longevity. OBJECTIVE: To assess the viability and potency of stromal vascular fraction (SVF) cells and adipose-derived stem cells (ASCs) in fat samples from lipoaspirates harvested with a novel 1470-nm diode, radial emitting LAL platform. Two processing methods, enzymatic and nonenzymatic, were compared. METHODS: Laser-assisted liposuction lipoaspirates harvested from 10 subjects were examined for cell viability after processing by enzymatic or nonenzymatic methods. Isolated SVF cells were cultured with an ASC-permissive medium to assess their viability and proliferation capacity by cell proliferation assay. Flow cytometric analysis with ASC-specific markers, gene expression levels, and immunofluorescence for ASC transcription factors were also conducted. RESULTS: Lipoaspirates showed high SVF cell viability of 97% ± 0.02% and 98% ± 0.01%, averaged SVF cell count of 8.7 × 10 6 ± 3.9 × 10 6 and 9.4 × 10 6 ± 4.2 × 10 6 cells per mL, and averaged ASC count of 1 × 10 6 ± 2.2 × 10 5 and 1.2 × 10 6 ± 5 × 10 5 cells per mL in nonenzymatic and enzymatic methods, respectively. The ASC-specific markers, gene expression levels, and immunofluorescence for ASC transcription factors confirmed the adipose origin of the cells. CONCLUSIONS: The laser lipoaspirates provide a high yield of viable and potent SVF cells and ASCs through both nonenzymatic and enzymatic processes. Improved purity of the harvested lipoaspirate and high ASC content are expected to result in extended graft longevity. Furthermore, eliminating enzymatic digestion may provide advantages, such as reducing process time, cost, and regulatory constraints.

The "CIV Classification," a New Proposal for the Architectural Grading of Vulvar Lichen Sclerosus.

OBJECTIVES: The purpose of this cross-sectional study was to prepare a reliable and easy-to-use architectural classification for vulvar lichen sclerosus (VLS) aimed at defining the morphological patterns of this condition. MATERIALS AND METHODS: An expert panel composed by 7 physicians with expertise in clinical care of vulvar conditions outlined the architectural criteria for the definition of VLS severity (phimosis of the clitoris, involvement of the interlabial sulci, narrowing of the vulvar introitus), identifying 5 grades to build up a classification. Thirteen physicians with 2-30 years expertise in vulvar diseases (nonexpert group) were asked to evaluate 3-5 pictures from 137 patients. Each physician individually assigned a grade to each case, according to the previously mentioned criteria. Interrater reliability was analyzed by means of intraclass correlation coefficient (ICC). The reliability concerning the 2 classifications of each rater was analyzed by means of κ statistic. Intraobserver and interobserver reliability in vivo was analyzed by means of κ index. RESULTS: This study provides a new classification of VLS, based on defined anatomical criteria and graded into mutually exclusive progressive classes.The ICC analysis showed a substantial interrater reliability of the classification, ICC = 0.89 (0.87-0.91), both in the expert panel and in the nonexpert group (ICC = 0.92 and 0.87, respectively). An "almost perfect" intraobserver and interobserver reliability was achieved among physicians in vivo (κ = 0.93). CONCLUSIONS: Our classification showed a high reliability. It is easy to use, and it can be applied in clinical practice and eventually, in the evaluation of regenerative and cosmetic surgery.

Defining the identity of human adipose-derived mesenchymal stem cells.

Adipose-derived mesenchymal stem cells (ADMSCs) are an ideal population for regenerative medical application. Both the isolation procedure and the culturing conditions are crucial steps, since low yield can limit further cell therapies, especially when minimal adipose tissue harvests are available for cell expansion. To date, a standardized procedure encompassing both isolation sites and expansion methods is missing, thus making the choice of the most appropriate conditions for the preparation of ADMSCs controversial, especially in view of the different applications needed. In this study, we compared the effects of three different commercial media (DMEM, aMEM, and EGM2), routinely used for ADMSCs expansion, and two supplements, FBS and human platelet lysate, recently proven to be an effective alternative to prevent xenogeneic antibody transfer and immune alloresponse in the host. Notably, all the conditions resulted in being safe for ADMSCs isolation and expansion with platelet lysate supplementation giving the highest isolation and proliferation rates, together with a commitment for osteogenic lineage. Then, we proved that the high ADMSC hematopoietic supportive potential is performed through a constant and abundant secretion of both GCSF and SCF. In conclusion, this study further expands the knowledge on ADMSCs, defining their identity definition and offers potential options for in vitro protocols for clinical production, especially related to HSC expansion without use of exogenous cytokines or genetic modifications.

Vulvar lichen sclerosus: A new regenerative approach through fat grafting.

OBJECTIVE. The aim of this study was to evaluate the efficacy of fat grafting in the treatment of severe vulvar lichen sclerosus (LS). Our primary outcome was to assess the improvement of mucocutaneous trophism, the resolution/reduction of symptoms, and the histological features of the vulvar skin after treatment. The secondary outcome was to evaluate the improvement in life quality, and in resumption and quality of sexual life. METHODS. Between 2011 and 2014, 36 patients were offered fat grafting to treat LS. Inclusion criteria were age between 25 and 80 years, histopathologic diagnosis of LS, good health, failure of previous first line treatments. RESULTS. 34 out of 36 patients (94%) showed a better vulvar trophismof the skin and mucosae; 27 (75%) had an improvement in caliber and elasticity of the vaginal introitus; clitoris burying degree was reduced in 18 patients (50%), 30 (83%) reported an increased volume of labia major a and minor a, 34 (94%) had a complete disappearance of scratching lesions, and 28 (78%) showed a remission of white lesions. Eventually 34 patients (95%) stopped using topical corticosteroids routinely. The improvement in life quality was significant for both DLQI (p b 0001) and FSFI (p b 0001). CONCLUSIONS. Fat grafting may have a role as a support and completion treatment in selected cases of women with vulvar LS who do not respond to first line therapy or in severe cases where the anatomical impairment does not allow a regular sexual function and a good quality of life.

Clinical Features and Management of Umbilical Endometriosis: A 30 Years' Monocentric Retrospective Study.

INTRODUCTION: Umbilical endometriosis (UE) is defined as the presence of endometrial-like tissue within the umbilicus and represents around 0.5-1% of all cases of endometriosis. UE is classified into primary or secondary UE. In this retrospective study, we aimed to assess symptoms, signs, recurrence rate of treated lesions, psychological wellbeing and health-related quality of life in women with UE. MATERIAL AND METHODS: We retrospectively reviewed all cases of women diagnosed with UE in the period 1990-2021 in our center. Post-operative recurrence of UE was considered as the reappearance of the umbilical endometriotic lesion, or as the recurrence of local symptoms in the absence of a well-defined anatomical recurrence of the umbilical lesion. Moreover, participants were invited to fill in standardized questionnaires on their health conditions. RESULTS: A total of 55 women with histologically proven UE were assessed in our center during the study period. At time of diagnosis, local catamenial pain and swelling were reported by 51% and 53.2% of women, respectively. A total of 46.8% of women reported catamenial umbilical bleeding. Concomitant non-umbilical endometriosis was identified in 66% of cases. As regards the treatment of UE, 83.6% of women underwent an en-bloc excision with histological confirmation of UE. During the follow-up period, 37 women (67.3%) agreed to undergo a re-evaluation. Recurrence of either umbilical symptoms, or umbilical nodule, was observed in 27% of patients, 11% of which did not receive post-operative hormonal therapy. Specifically, a recurrence of the umbilical endometriotic lesion was observed only in two women. Among the 37 women which we were able to contact for follow-up, 83.8% were satisfied with the treatment they had received. CONCLUSIONS: The high rate of patient satisfaction confirmed that surgical excision should be considered the gold standard treatment for umbilical endometriosis. Future studies should investigate the role of post-operative hormonal therapy, particularly in reducing the risk of symptom recurrence.

Umbilical Endometriosis: A Systematic Literature Review and Pathogenic Theory Proposal.

Umbilical endometriosis represents 30-40% of abdominal wall endometriosis and around 0.5-1.0% of all cases of endometriosis. The aim of this systematic review is to revisit the epidemiology, signs, and symptoms and to formulate a pathogenic theory based on literature data. We performed a systematic literature review using the PubMed and Embase databases from 1 January 1950 to 7 February 2021, according to the PRISMA guidelines. The review was registered at PROSPERO (CRD42021239670). Studies were selected if they reported original data on umbilical endometriosis nodule defined at histopathological examination and described as the presence of endometrial glands and/or stromal cells in the connective tissue. A total of 11 studies (10 retrospective and one prospective), and 14 case series were included in the present review. Overall, 232 umbilical endometriosis cases were reported, with the number per study ranging from 1 to 96. Umbilical endometriosis was observed in 76 (20.9%; 95% CI 17.1-25.4) of the women included in studies reporting information on the total number of cases of abdominal wall endometriosis. Umbilical endometriosis was considered a primary form in 68.4% (158/231, 95% CI 62.1-74.1) of cases. A history of endometriosis and previous abdominal surgery were reported in 37.9% (25/66, 95% CI 27.2-49.9) and 31.0% (72/232, 95% CI 25.4-37.3) of cases, respectively. Pain was described in 83% of the women (137/165, 95% CI 76.6-88.0), followed by catamenial symptoms in 83.5% (142/170, 95% CI, 77.2-88.4) and bleeding in 50.9% (89/175, 95% CI 43.5-58.2). In the 148 women followed for a period ranging from three to 92.5 months, seven (4.7%, 95% CI 2.3-9.4) recurrences were observed. The results of this analysis show that umbilical endometriosis represents about 20% of all the abdominal wall endometriotic lesions and that over two thirds of cases are primary umbilical endometriosis forms. Pain and catamenial symptoms are the most common complaints that suggest the diagnosis. Primary umbilical endometriosis may originate from implantation of regurgitated endometrial cells conveyed by the clockwise peritoneal circulation up to the right hemidiaphragm and funneled toward the umbilicus by the falciform and round liver ligaments.

Psychosexual Consequences of Female Genital Mutilation and the Impact of Reconstructive Surgery: A Narrative Review.

Purpose: We aim to provide a comprehensive overview of the health consequences of female genital mutilation/cutting (FGM/C), with a particular focus on the psychosexual implications of this practice and the overall impact of reconstructive plastic surgery. Methods: A MEDLINE search through PubMed was performed to identify the best quality evidence published studies in English language on long-term health consequences of FGM/C. Results: Women with FGM/C are more likely to develop psychological disorders, such as post-traumatic stress disorder, anxiety, somatization, phobia, and low self-esteem, than those without FGM/C. Most studies showed impaired sexual function in women with FGM/C. In particular, women with FGM/C may be physiologically less capable of becoming sexually stimulated than uncut women. Reconstructive surgery could be beneficial, in terms of both enhanced sexual function and body image. However, prospective studies on the impact of reconstructive surgery are limited, and safety issues should be addressed. Conclusion: Although it is clear that FGM/C can cause devastating immediate and long-term health consequences for girls and women, high-quality data on these issues are limited. Psychosexual complications need to be further analyzed to provide evidence-based guidelines and to improve the health care of women and girls with FGM/C. The best treatment approach involves a multidisciplinary team to deal with the multifaceted FGM/C repercussions.