Differential Capability of Clinically Employed Dermal Regeneration Scaffolds to Support Vascularization for Tissue Bioengineering

The loss of skin integrity has always represented a major challenge for clinicians dealing with dermal defects, such as ulcers (diabetic, vascular and chronic), postoncologic resections (i.e., radical vulvectomy) or dermatologic disorders. The introduction in recent decades of acellular dermal matrices (ADMs) supporting the repair and restoration of skin functionality represented a significant step toward achieving clean wound repair before performing skin grafts. Hard-to-heal ulcers generally depend on local ischemia and nonadequate vascularization. In this context, one possible innovative approach could be the prevascularization of matrices with vessel-forming cells (inosculation). This paper presents a comparative analysis of the most widely used dermal templates, i.e., Integra® Bilayer Matrix Wound Dressing, PELNAC®, PriMatrix® Dermal Repair Scaffold, Endoform® Natural Dermal Template, and Myriad Matrix®, testing their ability to be colonized by human adult dermal microvascular endothelial cells (ADMECs) and to induce and support angiogenesis in vitro and in vivo. By in vitro studies, we demonstrated that Integra® and PELNAC® possess superior pro-adhesive and pro-angiogenetic properties. Animal models allowed us to demonstrate the ability of preseeded ADMECs on Integra® to promote the engraftment, integration and vascularization of ADMs at the site of application.

What to do when nothing else is left to be done - metastatic non-HPV vulvar squamous cell carcinoma with multiple lines of chemotherapy

Recurrent vulvar squamous cell carcinoma with multiple site metastases is a rare entity – (up to 14.2% of the total number of recurrences), with a poor prognosis (only 15% of the patients alive at 5 years). Due to its “hard to find” character, there are no standardized guidelines available and the treatment is extrapolated from advanced cervical carcinoma, anal carcinoma and other squamous cell carcinomas. Immunotherapy has shown some positive results in vulvar carcinoma with PD-L1 positive, high TMB, high MSI or with MMR deficiency. An alternative for selected cases without therapeutic resources could be the HPV vaccine. We present the case of a 64-year-old woman diagnosed in 2014 with vulvar squamous cell carcinoma stage II for which she underwent radical vulvectomy with bilateral inguinal lymphadenectomy followed by external radiotherapy. In 2019 she developed local recurrence associated with lung, pleural, lymph nodes and subcutaneous metastasis, treated with three lines of chemotherapy: paclitaxel/carboplatin followed by cisplatin/5-fluorouracil and carboplatin/gemcitabine. The patient’s general health status altered progressively, and she died after the 4th cycle of carboplatin/gemcitabine. This case’s management could be a starting point for the vulvar carcinoma cases where the standard therapeutical options do not represent a choice anymore, providing the necessary example on how to approach it.

Radical vulvectomy for a rare case of squamous cell carcinoma vulva: a case report

Cancer of the vulva is the fourth most common malignancy of the female genital tract. Vulvar carcinoma is a rare and aggressive gynecological malignancy. It affects elderly females, with the mean age at diagnosis being 55-60 years. Regional metastasis to inguinal lymph nodes is common. There is a high incidence of pelvic node involvement, especially in those with pathologically positive inguinal nodes. Surgery appears to be the only curative treatment option in the early stages of the disease. But in most patients, surgery is associated with considerable morbidities and psychosexual issues. Hence, in the quest for a less morbid form of treatment, multimodality approaches with various combinations of surgery, chemotherapy, and radiation therapy have been suggested for advanced vulvar cancers. Due to the low incidence of the disease, the level of evidence for the success of these treatment modalities is poor. Mrs. X, a 54-year-old female, P2L2 A0 presented at Apollo hospitals, Ahmedabad with a giant vulvar tumor of about 8x7 cm in size arising from anterior half of vulva involving clitoris and both labia minora. The vulval growth was initially small and had attained present size in last 15 days. She had complaints of postmenopausal bleeding per vaginum for 8 days, foul smelling discharge and itching vulva on and off for 1 month. Biopsy revealed moderate to well differentiated squamous cell carcinoma (SCC). MRI pelvis with contrast found suspicious lymph node in bilateral iliac vessel region and bilateral inguinal region. She underwent radical vulvectomy with bilateral inguinal lymph node dissection, and bilateral pelvic lymph node dissection. Early diagnosis, timely intervention and prompt surgical management could save the patient’s life. Histopathological report showed well differentiated SCC of vulva with no lymphnodes involvement. Depth of tumor was 12 mm and there was no lymphovascular and perineural invasion. All surgical margins and base of growth were free of tumor. According to TNM stabilization patient had SCC vulva stage IB (T1bN0M0). This patient was disease free after 18 months of follow-up. Vulvar cancer incidence is significantly high in post-menopausal and multiparous women. The most important prognostic factors are tumor stage and lymph node status. Oncological resection should be equated with functional outcome. The multidisciplinary team approach should be sought for this rare gynecological malignancy.

Pembrolizumab in FIGO IVB Verrucous Carcinoma of the Vulva: A Case Report

BackgroundVulvar cancer is the fourth most common gynecologic cancer, and prognosis is poor in advanced vulvar cancer patients. Treatment for advanced vulvar cancer has not been satisfactory. In this report, we firstly report a FIGO IVB vulva verrucous carcinoma patient who obtained good prognosis after systemic treatment.Case PresentationA patient was admitted to hospital due to her vulvar lesion persistent for past 14 years. The vulvar mass has widely invaded urethra, part of anus, the lower third of the vagina, bilateral superior and inferior branches of pubis, and bilateral internal and external muscles of obturator. Multiple metastatic lymph nodes were also found in the pelvic cavity. The histopathological studies confirmed vulvar verrucous carcinoma with a PD-L1 overexpression. After six courses of neoadjuvant chemotherapy and pembrolizumab, the patient underwent radical vulvectomy and achieved optimal cytoreduction. Postoperative pathology found no residual tumor. The patient then received one course of postoperative chemotherapy and pembrolizumab, underwent radiation therapy, and was disease free after 6 months follow-up.ConclusionOur individualized treatment strategy is successful. Pembrolizumab is safe and effective in the treatment of advanced vulvar verrucous carcinoma with PD-L1 overexpression.