Selection of surgical strategies for vulvar Paget's disease.
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC8654428 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introductionand Importance: Extra Mammary Paget's disease (EMPD) of the vulva, a rare postmenopausal entity, is responsible for less than 1% of all vulvar neoplasms. Invasive EMPD of the vulva with underlying squamous cell carcinoma is even rare.Case presentationA 70-year-old para 5 postmenopausal lady presented with a history of vulvar itching and a gradually progressive reddish lesion on genitals unresolved by topical therapies for one year. Vulvar biopsy confirmed the presence of pagetoid cells with a focus of squamous invasion.DiscussionThe clinical presentation is often non-specific and typically presents as a pruritic skin rash in the vulva. Optimal management of EMPD of the vulva is unclear, but wide surgical excision is considered the standard therapeutic approach. Local recurrence in EMPD is common even with aggressive radical procedures. Constant follow-up is required to ensure early diagnosis of recurrences.ConclusionEarly biopsy of the suspicious eczematous lesion can help in definitive diagnosis and timely treatment of EMPD.
| S-EPMC8844793 | biostudies-literature
Project description:ObjectiveTo examine the effectiveness of topical imiquimod therapy for vulvar Paget's disease.MethodsA systematic literature search was conducted using three public search engines with entry keywords "Paget's disease" and "imiquimod". Case reports describing imiquimod treatment for vulvar Paget's disease were examined for demographics, treatment patterns, and outcome (63 cases).ResultsMedian age was 68, and nearly a half of cases were recurrent disease (50.8%) with surgical resection being the most common prior treatment modality (62.5%). All cases used 5% imiquimod and the median treatment duration was 4months. The most common initial treatment frequency was 3-4times/week (68.3%) followed by 5-7 (17.4%) and 1-2times/week (14.3%). Frequency-reduction due to adverse effects was seen in 9.5% with the initial 5-7times/week regimen being associated with the highest reduction rate (1-2, 3-4, and 5-7times/week: 0%, 2.3%, and 81.8%, p<0.01). In 46 (73.0%) cases, a complete remission (CR) to imiquimod therapy was reported, with 2, 4, and 6-month cumulative CR rates being 9.8%, 31.1%, and 71.6%, respectively. With median follow-up duration of 12months after the completion of imiquimod treatment, 2 (5.7%) of the 35 women who had a CR developed disease recurrence. Age, disease status (primary versus recurrent), and treatment frequency after dose reduction were not associated with CR rates (all, p>0.05).ConclusionOur results suggested that imiquimod therapy may be an effective possible treatment option for vulvar Paget's disease, especially for women who have experienced recurrence after multiple surgical resections or who are with poor surgical candidates.
| S-EPMC7521079 | biostudies-literature
Project description:•Invasive extramammary Paget's disease of the vulva is rare.•Distant metastasis has a very poor prognosis.•Given rarity of disease, no standardized treatment exists.•Single agent docetaxel is a viable treatment for metastatic invasive extramammary Paget's disease.
| S-EPMC9791582 | biostudies-literature
Project description:Paget's disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemic dissemination. Despite many years of intense research, the etiology of PDB has still to be conclusively determined. Based on a detailed review of genetic and viral factors incriminated in PDB, we propose a unifying hypothesis from which we can suggest emerging strategies and therapies. PDB results in weakened bone strength and abnormal bone architecture, leading to pain, deformity or, depending on the bone involved, fracture in the affected bone. The diagnostic assessment includes serum total alkaline phosphatase, total body bone scintigraphy, skull and enlarged view pelvis x-rays, and if needed, additional x-rays. The ideal therapeutic option would eliminate bone pain, normalize serum total alkaline phosphatase with prolonged remission, heal radiographic osteolytic lesions, restore normal lamellar bone, and prevent recurrence and complications. With the development of increasingly potent bisphosphonates, culminating in the introduction of a single intravenous infusion of zoledronic acid 5 mg, these goals of treatment are close to being achieved, together with long-term remission in almost all patients. Based on the recent pathophysiological findings, emerging strategies and therapies are reviewed: ie, pulse treatment with zoledronic acid; denosumab, a fully human monoclonal antibody directed against RANK ligand; tocilizumab, an interleukin-6 receptor inhibitor; odanacatib, a cathepsin K inhibitor; and proteasome and Dickkopf-1 inhibitors.
| S-EPMC3096538 | biostudies-literature
Project description:The aim is to analyse the clinical presentation, treatment and outcomes in patients with Paget's disease with invasive ductal carcinoma (PD-IDC), with special emphasis on the role of surgical treatment. Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, we investigated the differences in characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM) between patients with PD-IDC and those with invasive ductal carcinoma (IDC). Compared with IDC group, patients with PD-IDC had a better prognosis and lower mortality in adjusted analyses. In the multivariate analysis of cases with PD-IDC, history of ALND was significantly associated with OS while Her2 status were associated with BCSM. Further, subgroup analysis demonstrated no difference between surgical treatment subgroups for either OS or BCSM. The results demonstrated that PD-IDC appears to alter the association between prognosis and Her2 status. Meanwhile, breast-conserving surgery with radiotherapy may be a feasible treatment alternative and sentinel lymph node biopsy should be considered as an appropriate treatment for patients with PD-IDC.
| S-EPMC5395813 | biostudies-literature
Project description:Paget's disease (PD) is a chronic metabolically active bone disease, characterized by a disturbance in bone modelling and remodelling due to an increase in osteoblastic and osteoclastic activity. The vertebra is the second most commonly affected site. This article reviews the various spinal pathomechanisms and osseous dynamics involved in producing the varied imaging appearances and their clinical relevance. Advanced imaging of osseous, articular and bone marrow manifestations of PD in all the vertebral components are presented. Pagetic changes often result in clinical symptoms including back pain, spinal stenosis and neural dysfunction. Various pathological complications due to PD involvement result in these clinical symptoms. Recognition of the imaging manifestations of spinal PD and the potential complications that cause the clinical symptoms enables accurate assessment of patients prior to appropriate management.
| S-EPMC1934928 | biostudies-other
Project description:PURPOSE:To investigate patient-reported quality of life (QoL) and associated factors in vulvar cancer patients treated surgically by vulvar field resection (VFR) without adjuvant radiation. METHODS:We retrospectively evaluated patient-reported QoL as part of the prospective monocentric VFR trial using the 30-item European Organization for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30) supplemented by a question assessing sexual activity. All patients had been treated by VFR and no participant had received adjuvant radiotherapy. The gynecologic cancer lymphedema questionnaire (GCLQ) was used to determine the presence of lymphedema. Structured telephone interviews were conducted to assess postoperative sequelae and long-term complications. RESULTS:Forty-three VFR patients (median age 63 years) were available for QoL assessment. Thirty-eight (88%) had received inguinal lymph-node dissection in addition to VFR. Mean global QoL (global health status) rating among all patients was 66.1 (± 25.5) on a scale from 0 to 100 with higher scores indicating better QoL. Higher GCLQ scores were significantly associated with lower global QoL scores (Spearman's rank correlation ρ =- 0.7, p < 0.0001). The presence of preoperative co-morbidities and postoperative wound-healing complications were also linked to reduced QoL (p < 0.01 for both). In a multivariable regression model, there was a significant interaction between preoperative co-morbidities and wound-healing complications with regard to global QoL (p < 0.05). CONCLUSION:Overall, VFR patients exhibit good quality of life postoperatively. The presence of lymphedema, wound-healing complications, and preoperative morbidities were associated with reduced QoL. Prospective longitudinal studies have to confirm our findings in the future.
| S-EPMC7266857 | biostudies-literature
Project description:Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. The current evidence suggests that this likely results from a combination of delayed diagnosis and different tumor biology, treatment strategies, and treatment response. Although many landmark trials on checkpoint inhibitors included mucosal and vulvar melanomas, the results were often not reported separately. Post-hoc analyses indicate overall response rates between 19 and 37% for checkpoint inhibitors. A recently published retrospective study on vulvar melanomas suggests an objective response in 33.3% with a similar safety profile to cutaneous melanoma. Tyrosine kinase inhibitors may be considered in recurrent disease if a c-KIT mutation is present.
| S-EPMC8421300 | biostudies-literature
Project description:Paget's disease of bone (PDB) is a common metabolic bone disease characterised by focal areas of increased bone turnover, which primarily affects people over the age of 55 years. Genetic factors have a fundamental role in the pathogenesis of PDB and are probably the main predisposing factor for the disease. The genetic contribution to PDB susceptibility ranges from rare pathogenic mutations in the single gene SQSTM1 to more common, small effect variants in at least seven genetic loci that predispose to the disease. These loci have additive effects on disease susceptibility and interact with SQSTM1 mutations to affect disease severity, making them a potentially useful tool in predicting disease risk and complication and in managing treatments. Many of these loci harbour genes that have important function in osteoclast differentiation such as CSF1, DCSTAMP and TNFRSF11A. Other susceptibility loci have highlighted new molecular pathways that have not been previously implicated in regulation of bone metabolism such as OPTN, which was recently found to negatively regulate osteoclast differentiation. PDB-susceptibility variants exert their effect either by affecting the protein coding sequence such as variants found in SQSTM1 and RIN3 or by influencing gene expression such as those found in OPTN and DCSTAMP. Epidemiological studies indicate that environmental triggers also have a key role in PDB and interact with genetic factors to influence manifestation and severity of the disease; however, further studies are needed to identify these triggers.
| S-EPMC4635861 | biostudies-literature
Project description:Paget's disease of bone is characterized by highly localized areas of increased bone resorption accompanied by exuberant, but aberrant new bone formation with the primary cellular abnormality in osteoclasts. Paget's disease provides an important paradigm for understanding the molecular mechanisms regulating both osteoclast formation and osteoclast-induced osteoblast activity. Both genetic and environmental etiologies have been implicated in Paget's disease, but their relative contributions are just beginning to be defined. To date, the only gene with mutations in the coding region linked to Paget's disease is sequestosome-1 (SQSTM1), which encodes the p62 protein, and these mutations lead to elevated cytokine activation of NF-B in osteoclasts but do not induce a "pagetic osteoclast" phenotype. Further, genetic mutations linked to Paget's appear insufficient to cause Paget's disease and additional susceptibility loci or environmental factors may be required. Among the environmental factors suggested to induce Paget's disease, chronic measles (MV) infection has been the most studied. Expression of the measles virus nucleocapsid gene (MVNP) in osteoclasts induces pagetic-like osteoclasts and bone lesions in mice. Further, mice expressing both MVNP in osteoclasts and germline mutant p62 develop dramatic pagetic bone lesions that were strikingly similar to those seen in patients with Paget's disease. Thus, interactions between environmental and genetic factors appear important to the development of Paget's disease. In this article we review the mechanisms responsible for the effects of mutant p62 gene expression and MVNP on osteoclast and osteoblast activity, and how they may contribute to the development of Paget's disease of bone.
| S-EPMC4075272 | biostudies-literature