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Age and Ageing May 2023previous studies have focused on the risk of cardiovascular disease (CVD)-related death in individual cancers, adolescents or all cancers.
BACKGROUND
previous studies have focused on the risk of cardiovascular disease (CVD)-related death in individual cancers, adolescents or all cancers.
OBJECTIVE
to evaluate the risk of CVD-related death in older patients with cancer.
METHODS
older patients with cancer (over 65 years) of 16 cancers diagnosed between 1975 and 2018 were screened out from the Surveillance, Epidemiology and End Results program. The proportion of deaths, competing risk regression models, standardized mortality ratios (SMRs) and absolute excess risks (AERs) were used to assess the risk of CVD-related death.
RESULTS
this study included 1,141,675 older patients (median follow-up: 13.5 years). Of the 16 individual cancers, the risk of CVD death exceeded primary neoplasm death in older patients with cancers of the breast, endometrium, vulva, prostate gland, penis and melanoma of the skin over time (high competing risk group). Compared to the general older population, older patients with cancer had higher SMR and AER of CVD-related death (SMR: 1.58-4.23; AER: 21.16-365.89), heart disease-related death (SMR: 1.14-4.16; AER: 16.29-301.68) and cerebrovascular disease-related death (SMR: 1.11-4.66; AER: 3.02-72.43), with the SMR trend varying with CVD-related death competing risk classifications. The risk of CVD-related death in the high-competing risk group was higher than in the low-competing risk group.
CONCLUSIONS
for older patients with cancer, six of 16 individual cancers, including breast, endometrium, vulva, prostate gland, penis and melanoma of the skin was at high risk of CVD-related death. Management for long-term cardiovascular risk in older patients with cancer is needed.
Topics: Male; Female; Humans; Adolescent; Aged; Cause of Death; Cardiovascular Diseases; Heart Diseases; Risk Factors; Melanoma
PubMed: 37192506
DOI: 10.1093/ageing/afad068 -
Biomedicines Jun 2021Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can... (Review)
Review
Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can distinguish melanomas originating in the mucous membranes and located in areas not exposed to the sun, namely the vulvo-vaginal melanomas. By contrast with cutaneous melanomas, the incidence of these types of melanomas is constant, being diagnosed in females in their late sixties. While hairy skin and glabrous skin melanomas of the vulva account for 5% of all cancers located in the vulva, melanomas of the vagina and urethra are particularly rare conditions. The location in areas less accessible to periodic inspection determines their diagnosis in advanced stages, often metastatic. Moreover, despite the large number of drugs newly approved in recent decades for the treatment of cutaneous melanoma, especially in the category of biological drugs, the mortality of vulvo-vaginal melanomas has remained almost constant. This, together with the absence of specific treatment guidelines due to the lack of a sufficient number of cases to conduct randomized clinical trials, makes melanomas with this localization a discouraging diagnosis, associated with a very poor prognosis. Our aim is therefore to draw attention to this oftentimes overlooked entity in order to encourage the community to employ various strategies meant to increase research in this area. By highlighting the main risk factors of vulvar and vaginal melanomas, as well as the clinical manifestations and molecular changes underlying these neoplasms, ideally novel therapeutic schemes will, in time, be brought into effect.
PubMed: 34209084
DOI: 10.3390/biomedicines9070758 -
Melanoma Research Aug 2023Malignant vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of rare malignant melanomas with critical biological properties that differ from... (Observational Study)
Observational Study
Malignant vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of rare malignant melanomas with critical biological properties that differ from other cancers. In Japan, adequate surveys have yet to be conducted. This study aimed to elucidate the clinicopathological demographics and outcomes of VuM and VaM in Japan. This retrospective observational study included women with invasive VuM or VaM identified from older medical records in Japan. We collected clinical data and used the Kaplan-Meier method to analyze progression-free survival (PFS) and overall survival (OS). Univariate and multivariate regression models were used to identify factors significantly related to survival. We identified 217 patients, 109 (50.2%) with VuM and 108 (49.8%) with VaM. The median PFS was 16.8 months in patients with VuM [95% confidence interval (CI), 23.1-87.7] and 15.6 months in those with VaM (95% CI, 8.4-12.6). The median OS was 43.9 months (95% CI, 60-138) and 31.1 months (95% CI, 24.8-45.3) in patients with VuM and VaM, respectively. Multivariate analysis showed that a disease stage higher than stage III, based on the American Joint Committee on Cancer (AJCC) guidelines, was associated with poorer PFS [hazard ratio (HR), 2.063; 95% CI, 0.995-4.278] and an unknown surgical margin was the only independent factor influencing OS (HR, 2.188; 95% CI, 1.203-3.977). The overall outcomes of invasive VuM and VaM in Japan remain poor. AJCC staging and surgical margins were significant predictors of survival.
Topics: Humans; Female; Melanoma; Skin Neoplasms; Japan; Vaginal Neoplasms; Vulvar Neoplasms; Vagina; Vulva; Demography; Retrospective Studies; Neoplasm Staging; Prognosis; Melanoma, Cutaneous Malignant
PubMed: 37162526
DOI: 10.1097/CMR.0000000000000894 -
Journal of the National Comprehensive... Mar 2024Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to...
Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.
Topics: Female; Humans; Adenocarcinoma; Genital Neoplasms, Female; Paget Disease, Extramammary; Skin Neoplasms; Vulvar Neoplasms
PubMed: 38503056
DOI: 10.6004/jnccn.2024.0013 -
Journal of Lower Genital Tract Disease Jan 2023Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they...
OBJECTIVES
Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they have impacted cancer treatment, an understanding of recent innovations in the molecular features of vulvar lesions is important.
MATERIALS AND METHODS
Systematic literature search was performed on PubMed, Google Scholar, and Scopus databases for molecular and genetic characteristics of vulvar neoplasms. Peer-reviewed literature published in English is included.
RESULTS
Squamous cell carcinoma (SCC) and its precursors are the predominant neoplasm at this site. Human papillomavirus (HPV) plays a crucial role in the pathogenesis of some of these lesions. Human papillomavirus-associated SCC follows the carcinogenic pathway driven by viral proteins E6 and E7 while HPV-independent SCC shows a high incidence of mutation of TP53 and CDKN2A genes. Mutations in the genes involving the PI3K-Akt pathway play an important role in the pathogenesis of both types of SCC. Among other vulvar malignancies, melanoma, and vulvar Paget disease (VPD) pose a significant clinical challenge and have unique molecular characteristics. Compared with dermal cutaneous melanoma, vulvar melanoma shows a higher rate of mutation of cKIT and NRAS genes and a lower rate of mutations in BRAF . Less than 20% of VPD shows amplification of ERBB2 and seldom shows mutation in genes involving the PI3K-Akt pathway.
CONCLUSIONS
Several potentially targetable molecular pathways have emerged as they have been shown to be involved in the tumorigenesis of SCC, melanoma, and VPD.
Topics: Female; Humans; Carcinoma, Squamous Cell; Human Papillomavirus Viruses; Melanoma; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Skin Neoplasms; Vulvar Neoplasms
PubMed: 36083687
DOI: 10.1097/LGT.0000000000000701 -
International Journal of Gynecological... Sep 2023To investigate the utilization and outcomes of adjuvant immunotherapy for patients with vulvar melanoma and inguinal lymph node metastases.
OBJECTIVE
To investigate the utilization and outcomes of adjuvant immunotherapy for patients with vulvar melanoma and inguinal lymph node metastases.
METHODS
The National Cancer Database was accessed and patients with vulvar melanoma diagnosed between 2004 and 2015 who did not have distant metastases, underwent inguinal lymphadenectomy, had positive lymph nodes, and at least 1 month of follow-up were identified. Administration of immunotherapy was evaluated and clinicopathological characteristics were compared. Median overall survival was compared with the log-rank test. Stratified analysis based on clinical status of lymph nodes was performed. A Cox model was constructed to evaluate survival after controlling for confounders.
RESULTS
A total of 300 patients were identified; the rate of immunotherapy use was 25% (75 patients). Patients who received immunotherapy were younger (median 58 vs 70 years, p<0.001); however, the two groups were comparable in terms of clinical lymph node status, rate of positive tumor margins, presence of tumor ulceration, tumor size, Breslow thickness, and performance of comprehensive lymphadenectomy. There was no overall survival difference between patients who did (median 31.08 months) and did not (median 22.77 months) receive immunotherapy (p=0.18). Following stratification by clinical lymph node status, immunotherapy did not improve overall survival of patients with clinically negative (median 35.35 vs 33.22, p=0.75) or positive lymph nodes (median 23.33 vs 16.99, p=0.64). After controlling for confounders, administration of immunotherapy was not associated with better overall survival (HR 0.81, 95% CI 0.57 to 1.14).
CONCLUSIONS
In this study approximately one in four patients received adjuvant immunotherapy. Immunotherapy was not associated with improved overall survival.
Topics: Humans; Female; Melanoma; Vulvar Neoplasms; Databases, Factual; Immunotherapy; Lymph Nodes
PubMed: 37666537
DOI: 10.1136/ijgc-2023-004696 -
Histopathology Jul 2023Extramammary Paget disease (EMPD) is an epithelial neoplasm that can occur at many sites, including the vulva and scrotum. EMPD is characterised by the presence of...
AIMS
Extramammary Paget disease (EMPD) is an epithelial neoplasm that can occur at many sites, including the vulva and scrotum. EMPD is characterised by the presence of neoplastic cells, in single cells and clusters, that infiltrate all layers of non-neoplastic squamous epithelium. The differential diagnosis for EMPD includes melanoma in situ and secondary involvement of tumours from other sites, such as urothelial or cervical; pagetoid spread of tumor cells can also been seen at other sites, such as anorectal mucosa. The most frequently utilised biomarkers for confirming the diagnosis of EMPD include CK7 and GATA3; however, these biomarkers lack specificity. The purpose of this study was to evaluate TRPS1, a newly described breast biomarker, in pagetoid neoplasms of the vulva, scrotum and anorectum.
METHODS AND RESULTS
Fifteen cases of primary EMPD of the vulva (two with associated invasive carcinoma) and four primary EMPD of the scrotum showed strong nuclear immunoreactivity for TRPS1. In contrast, five cases of vulvar melanoma in situ, one case of urothelial carcinoma with secondary pagetoid spread into the vulva and two anorectal adenocarcinomas with pagetoid spread into anal skin (one with associated invasive carcinoma) were negative for TRPS1. Additionally, weak nuclear TRPS1 staining was observed in non-neoplastic tissues (e.g. keratinocytes), but always with less intensity when compared to tumour cells.
CONCLUSIONS
These results demonstrate that TRPS1 is a sensitive and specific biomarker for EMPD, and may be especially useful for excluding secondary involvement of the vulva by urothelial and anorectal carcinomas.
Topics: Male; Female; Humans; Carcinoma, Transitional Cell; Paget Disease, Extramammary; Biomarkers, Tumor; Urinary Bladder Neoplasms; Melanoma; Repressor Proteins; Melanoma, Cutaneous Malignant
PubMed: 36971374
DOI: 10.1111/his.14908 -
Modern Pathology : An Official Journal... Dec 2022Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions,...
Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions, mutations, and copy number changes, were performed on 750 melanomas (375 primary and 375 metastases) at our institution from 2014-2021. These included 599 (80%) cutaneous, 38 (5%) acral, 11 (1.5%) anorectal, 23 (3%) sinonasal, 27 (3.6%) eye (uveal/ conjunctiva), 11 (1.5%) genital (vulva/penile), and 41 (5.5%) melanomas of unknown primary. Sixteen fusions (2%) were detected in samples from 16 patients: 12/599 (2%) cutaneous, 2/38 (5%) acral, 1/9 (11%) vulva, 1/23(4.3%) sinonasal; and 12/16 (75%) fusions were potentially targetable. We identified two novel rearrangements: NAGS::MAST2 and NOTCH1::GNB1; and two fusions that have been reported in other malignancies but not in melanoma: CANT1::ETV4 (prostate cancer) and CCDC6::RET (thyroid cancer). Additional fusions, previously reported in melanoma, included: EML4::ALK, MLPH::ALK, AGAP3::BRAF, AGK::BRAF, CDH3::BRAF, CCT8::BRAF, DIP2B::BRAF, EFNB1::RAF1, LRCH3::RAF1, MAP4::RAF1, RUFY1::RAF1, and ADCY2::TERT. Fusion positive melanomas harbored recurrent alterations in TERT and CDKN2A, among others. Gene fusions were exceedingly rare (0.2%) in BRAF/RAS/NF1-mutant tumors and were detected in 5.6% of triple wild-type melanomas. Interestingly, gene rearrangements were significantly enriched within the subset of triple wild-type melanomas that harbor TERT promoter mutations (18% versus 2%, p < 0.0001). Thirteen (81%) patients were treated with immunotherapy for metastatic disease or in the adjuvant setting. Six of 12 (50%) patients with potentially actionable fusions progressed on immunotherapy, and 3/6 (50%) were treated with targeted agents (ALK and MEK inhibitors), 2 off-label and 1 as part of a clinical trial. One patient with an AGAP3::BRAF fusion positive melanoma experienced a 30-month long response to trametinib. We show that, detecting fusions, especially in triple wild-type melanomas with TERT promoter mutations, may have a clinically significant impact in patients with advanced disease who have failed front-line immunotherapy.
Topics: Male; Female; Humans; Proto-Oncogene Proteins B-raf; Melanoma; Gene Fusion; Mutation; Receptor Protein-Tyrosine Kinases; Nerve Tissue Proteins
PubMed: 35871080
DOI: 10.1038/s41379-022-01138-z -
Urologic Oncology Jan 2023Inguinal lymph node dissection (ILND) is an essential step in both treatment and staging of several malignancies including penile and vulvar cancers. Various open, video... (Review)
Review
BACKGROUND
Inguinal lymph node dissection (ILND) is an essential step in both treatment and staging of several malignancies including penile and vulvar cancers. Various open, video endoscopic, and robotic-assisted techniques have been utilized so far. In this review, we aim to describe available minimally invasive surgical approaches for ILND, and review their outcomes and complications.
METHODS
The PubMed, Wiley Online Library, and Science Direct databases were reviewed in February 2020 to find relevant studies published in English within 2000-2020.
FINDINGS
There are different minimally invasive platforms available to accomplish dissection of inguinal nodes without jeopardizing oncological results while minimizing postoperative complications. Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy are safe and achieve the same nodal yield, a surrogate metric for oncological adequacy. When compared to open technique, Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy may offer faster postoperative recovery and fewer postoperative complications including wound dehiscence, necrosis, and infection. The relatively high rate and severity of postoperative complications hinders utilization of recommended ILND for oncologic indications. Minimally invasive approaches, using laparoscopic or robotic-assisted platforms, show some promise in reducing the morbidity of this procedure while achieving adequate short and intermediate term oncological outcomes.
Topics: Male; Humans; Penile Neoplasms; Inguinal Canal; Video-Assisted Surgery; Lymph Node Excision; Laparoscopy; Robotics; Postoperative Complications; Lymph Nodes
PubMed: 32855056
DOI: 10.1016/j.urolonc.2020.07.026 -
Bulletin Du Cancer Jun 2020Sentinel node is defined as the first node to receive drainage from a primary tumor and seems to reflect the nodal status in the lymphatic drainage of the tumor.... (Review)
Review
Sentinel node is defined as the first node to receive drainage from a primary tumor and seems to reflect the nodal status in the lymphatic drainage of the tumor. Sentinel node technique has modified the pathological examination of lymph nodes, with intraoperative evaluation of sentinel node, allowing immediate lymph node dissection in case of positive sentinel node, and histological ultrastratification to detect occult metastases. This is a literature review of different histological protocols of sentinel node according to different organs. Except for sentinel node in breast cancer and melanoma, intraoperative examination of sentinel node is helpful using frozen section, more sensitive than touch imprint cytology. Sentinel node should be embedded in paraffin block entirely after gross sectioning at two millimeters intervals parallel to the long axis of the node. Histological ultrastaging with serial sections can be helpful, but the number of sections and the interval between them is not codified. Three sections at 200-250 microns can identify the majority of micrometastases (<2mm and >200 microns). Systematic immunohistochemistry of sentinel node is not necessary for breast cancers, since isolated tumor cells do not modify the therapeutic strategy, but remains useful in other organs.
Topics: Breast Neoplasms; Endometrial Neoplasms; Female; Frozen Sections; Humans; Intraoperative Period; Lymph Node Excision; Melanoma; Neoplasms; Sentinel Lymph Node; Skin Neoplasms; Uterine Cervical Neoplasms; Vulvar Neoplasms
PubMed: 32037014
DOI: 10.1016/j.bulcan.2019.11.003