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Therapy for Primary Vulvar Carcinoma.

ABSTRACT: The rather rare vulvar cancer is almost always a squamous cell carcinoma that mostly develops from an underlying VIN or HPV infection. In addition, lichen sclerosus et atrophicans, immune deficiency, nicotine abuse or anogenital intraepithelial neoplasias may play a role in the pathogenesis. Surgical therapy aims at an R0 resection in the sense of a complete vulvectomy or a radical local excision with, if necessary, plastic reconstruction. Also, the vulvar field resection with consideration of the compartment model has been discussed. Besides the classic inguinofemoral lymphadenectomy, in selected cases of vulvar cancer sentinel biopsies are performed by experienced surgeons in the larger centres. In contrast, systemic therapy plays only a subordinate role; in isolated cases down-staging by means of neoadjuvant chemotherapy may be useful. However, there is at present no indication for adjuvant chemotherapy. Neoadjuvant radiochemotherapy is also not to be recommended on account of its unfavourable ratio of efficacy to side effects. On the other hand adjuvant radiotherapy is indicated in cases of positive inguinal lymph nodes. According to the current data the indication should be made generously in such cases.

SUBMITTER: Herr D

PROVIDER: S-EPMC4024610 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other

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Therapy for Primary Vulvar Carcinoma.

Herr D D Juhasz-Boess I I Solomayer E F EF

Geburtshilfe und Frauenheilkunde 20140301 3

The rather rare vulvar cancer is almost always a squamous cell carcinoma that mostly develops from an underlying VIN or HPV infection. In addition, lichen sclerosus et atrophicans, immune deficiency, nicotine abuse or anogenital intraepithelial neoplasias may play a role in the pathogenesis. Surgical therapy aims at an R0 resection in the sense of a complete vulvectomy or a radical local excision with, if necessary, plastic reconstruction. Also, the vulvar field resection with consideration of t ...[more]

PMID: 24882877

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Project description:The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14-15.87, p = 0.03) and 2.68 (CI 95% = 1.0-7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.

Project description:Although oncogynaecological management of bulky vulvar tumors tends to minimally-invasive approaches preceded by neoadjuvant therapies, ultra-radical surgery with curative intent may still have an important role. These procedures remain associated with significant short and long-term complications, imposing the need for novel reconstructive techniques [Brown et al., 2017, Di Donato et al., 2017, Moreno-Palacios et al., 2015, Oonk et al., 2017]. We present a video highlighting the crucial surgical steps of a successful pelvic exenterative procedure followed by perineal reconstruction with a muscle-sparing flap technique. A 72-year woman with history of stage II vulvar epidermoid carcinoma, treated with radical surgery and adjuvant radiotherapy. At two-year follow-up local recurrence was diagnosed, handled with large excisional surgical treatment. Within four years a second local recurrence occurred, with infiltrative and bulky dimensions extending to perianal region and vaginal wall. A multidisciplinary surgical approach with curative intent was performed, involving gynecologists, colorectal and plastic surgeons: radical bilateral vulvectomy with distal colpectomy, abdominoperineal resection with colostomy, perineal reconstruction with deep inferior epigastric perforators (DIEP) flap. No major intraoperative or postoperative complications occurred, and the patient was discharged within two weeks with no readmissions for wound care. At two-year follow up she remains in complete remission of the disease. No flap complications occurred during this period. In highly selected patients with recurrent vulvar cancer previously submitted to multiple surgeries and radiotherapy, pelvic exenterative procedures followed by reconstructive techniques allow free surgical margins minimizing morbidity and pelvic disfiguring surgery. Association of reconstructive techniques to radical vulvo-vaginal surgery can shift the paradigm of oncological treatment approach, improving outcomes and quality-of-life.

Dataset Information

Therapy for Primary Vulvar Carcinoma.

Publications

Therapy for Primary Vulvar Carcinoma.

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