Management of primary and recurrent Bartholin's gland carcinoma: A systematic review on behalf of MITO Rare Cancer Group.

Bartholin gland carcinoma is an extremely rare disease. Information regarding treatment is scarce and there is no strict consensus on best practice. All studies reporting cases of Bartholin's gland cancer were screened and evaluated for inclusion. Baseline characteristics of studies were extracted. A total number of 290 manuscripts collected were available for the review process. Studies included in a previous systematic review were not duplicated. In total, details of 367 patients were collected, as follows: histological features, clinical presentation, treatment, recurrent rate, treatment of recurrence and outcome. About 35% of Bartholin gland carcinoma were squamous cell carcinoma. Almost 50% of patients presented with advanced stage. The therapeutic approach was mainly surgery, and in 61% of those women lymph node assessment was performed. Recurrence occurred in 21% of cases. Bartholin gland cancer remains a challenge for gynecologic oncologists. Guidelines, centralization to referral centers and standardized therapy are needed.

An update on current pharmacotherapy for vulvar cancer.

INTRODUCTION: Limited data on the role of pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer are available. AREAS COVERED: This article aims to provide an overview of the current treatment options for patients with vulvar cancer. PubMed (MEDLINE), Embase, CENTRAL, Scopus, and Web of Science databases, as well as ClinicalTrials.gov were searched to review the current evidence as well as future perspectives on the role of pharmacotherapy in patients with vulvar carcinoma. EXPERT OPINION: There has been no consensus on the pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer. Concurrent platinum-based chemoradiation is the most widely used treatment modality for primary treatment or for neoadjuvant settings. Chemotherapy in metastatic disease is considered a palliative treatment. Anti-EGFR tyrosine kinase inhibitors seem to show promising anti-tumor activity in patients harboring EGFR alteration. Similarly, growing evidence supports the adoption of immune checkpoint inhibitors in both neoadjuvant and metastatic settings. Molecular and genomic profiling is advocated to identify target mutations. The PI3K/AKT/mTOR and HER/ErbB pathways might represent two intriguing treatment options. Treatments directed against HPV are discussed as well. Further evidence is warranted to identify the best treatment modalities for patients with locally advanced, recurrent, and metastatic disease.

PARP Inhibitors in Newly Diagnosed and Recurrent Ovarian Cancer.

Ovarian cancer is the most lethal gynecologic malignancy, characterized by a high death-to-incidence ratio. Platinum-based chemotherapy is the mainstay of treatment for newly diagnosed and platinum-sensitive recurrent ovarian cancer. Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) have been incorporated into the treatment strategy for ovarian cancer. PARP inhibitors showed particular benefit for patients harboring defects in DNA repair pathways. Accumulating evidence showed that PARP inhibitors provide a benefit in newly diagnosed advanced ovarian cancer, even in the absence of BRCA mutation, as reported in the PRIMA, PRIME, and ATHENA-mono trials. Interestingly, the PAOLA-1 study provides another important finding, supporting the adoption of olaparib plus bevacizumab in patients with homologous recombination deficiency. Although those results are exciting, several patients develop resistance to PARP inhibitors. Hence, new combinations are under investigation to identify new treatment strategies to overcome this resistance. Currently, researchers are focused on the possibility to adopt PARP inhibitors even in the setting of platinum-resistant disease. The present critical review aims to report the current landscape and further perspective for strengthening PARP inhibitors' effectiveness in newly diagnosed and recurrent ovarian cancer.

Chemo-surgical approach in vulvar leiomyosarcoma: A case report.

INTRODUCTION: Primary sarcoma of the vulva is an extremely rare entity, representing only 1%-3% of all vulvar malignant neoplasms. Among sarcomas, leiomyosarcoma (LMS) is the most prevalent histologic variant. Due to the rarity of LMS, guidelines are lacking and phase III trials have not been carried out, so clinical management is based on local clinical practice and physician experience. CASE PRESENTATION: Here, we described a case of primary LMS of the vulva and its successful management, with the adoption of neoadjuvant chemotherapy and surgery. We report a case of a 74-year-old woman with 12.5 cm vulvar LMS. The patient received three cycles of neoadjuvant chemotherapy with a partial response. Radical vulvectomy with vulvar reconstruction with V-F flap was carried out. Surgical margins were negative. Three additional cycles of adjuvant chemotherapy were delivered. RESULTS: One year after treatment, the patient was disease-free. CONCLUSION: There are no approved therapeutic protocols for this rare neoplasia. Surgery is the mainstay of treatment. However, it is not always feasible, so neoadjuvant chemotherapy was delivered for downstaging the vulvar lesion. We suppose that neoadjuvant chemotherapy has optimized the possibilities of radical surgery. Despite the anectodical nature of this case presentation, neoadjuvant chemotherapy seems a valid therapeutic option for managing patients with bulky vulvar sarcoma. Further large collaborative studies are warranted to identify the best therapeutic option for these patients.

Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment.

OBJECTIVE: In the present review, the different phenotypes, clinimetric and imaging tools able to assess joint involvement in patients affected by Systemic Lupus Erythematosus (SLE) have been described and summarized. Furthermore, the current knowledge about the pathogenic mechanism and the potential biomarkers of this feature is reported. METHODS: A literature search was done in PubMed, accessed via the National Library of Medicine PubMed interface (http://www.ncbi.nlm.nih.gov/pubmed). Firstly, PubMed was searched using the term "systemic lupus erythematosus" OR "lupus" in combination with (AND) "joint" OR "articular".Secondly, the same PubMed research was combined with other terms, such as "pathogenesis" OR "genetic" OR "antibodies" OR "biomarkers" OR "cytokines" OR "imaging" OR "ultrasonography" OR "magnetic resonance" OR "clinimetry". RESULTS: After a stringent selection, we evaluated in the present review 13 papers concerning clinical phenotypes of SLE joint involvement, 14 concerning clinimetric assessment, 20 concerning imaging, and finally, 28 concerning pathogenesis and biomarkers. Further relevant data were obtained from the reference lists of articles returned using these search terms and from authors own experience and knowledge of the literature. CONCLUSION: Despite the prevalence and severity of SLE joint involvement, more awareness and a deeper evaluation of the clinical heterogeneity of this manifestation are mandatory. Moreover, longitudinal studies are needed to assess the progression of this manifestation and to provide standard definitions and examination/recording protocols.

Early detection of podiatric anomalies in children with Down syndrome.

AIMS: To verify the importance of podiatric evaluation in patients with Down syndrome for the early diagnosis and treatment of minor orthopaedic problems. METHODS: Case-control study of 50 children affected by Down syndrome (aged 4-10 y) without major orthopaedic malformations compared to 100 healthy children. A complete podiatric examination was performed on all patients and controls. RESULTS: Children with Down syndrome showed several orthopaedic anomalies including bony deformity of the forefoot (90%), flat foot (60%), isolated calcaneal valgus (24%), knee valgus (22%) and pronated flat foot (16%). These abnormalities were responsible for postural alterations as confirmed by baropodometric examination. CONCLUSION: The data demonstrated a greater incidence of minor orthopaedic alterations and suggest the necessity of regular podiatric examinations in the follow-up of this syndrome.