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Journal of Clinical Medicine Jun 2024Human papilloma virus (HPV) infection and the management of its persistence is still a great medical challenge. Recently, scientific evidence has supported the...
Human papilloma virus (HPV) infection and the management of its persistence is still a great medical challenge. Recently, scientific evidence has supported the potential therapeutic effects of four combined natural molecules-epigallocatechin gallate (EGCG), folic acid, vitamin B12 and hyaluronic acid (HA)-in counteracting HPV DNA positivity and related cytological lesions. : Each patient of these five clinical cases had persistent HPV positivity in the anogenital site and assumed a dietary supplement based on a combination of 200 mg of EGCG, 50 mg of HA, 1 mg of vitamin B12 and 400 mcg of folic acid (Pervistop, Farmares s.r.l., Rome, Italy) at a dosage of 1 or 2 caps/day for 6 or 3 months, respectively, depending on clinical history. : After treatment, all the patients reported a negative HPV DNA test and improved cytological lesions, thus demonstrating the ability of these combined molecules to counteract both anal and cervical HPV infection and related manifestations. : Overall, these data corroborate previous evidence about the effectiveness of such natural molecules in the management of HPV infection and its persistence. Naturally, further studies with a larger population and long-term follow-up will contribute to reinforce the positive effects of this dietary supplement in counteracting HPV infection.
PubMed: 38930126
DOI: 10.3390/jcm13123597 -
Cancers Jun 2024High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex...
High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series.
PubMed: 38927976
DOI: 10.3390/cancers16122268 -
Histopathology Jun 2024Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and... (Review)
Review
Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplastic entities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed.
PubMed: 38923027
DOI: 10.1111/his.15252 -
The Journal of Pathology Jun 2024SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse...
SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression-free survival independent of other major clinical and pathological features. A mouse model engineered for Kras expression in the adult oral epithelium induced benign papillomas, however the combination of Kras with loss of epithelial Smad4 expression resulted in rapid development of invasive carcinoma with features of human OSCC. Examination of regulatory pathways in 3D organoid cultures of SMAD4+ and SMAD4- mouse tumors with Kras mutation found that either loss of SMAD4 or inhibition of TGFβ signaling upregulated the WNT pathway and altered the extracellular matrix. The gene signature of the mouse tumor organoids lacking SMAD4 was highly similar to the gene signature of human head and neck squamous cell carcinoma. In summary, this work has uncovered novel mechanisms by which SMAD4 acts as a tumor suppressor in OSCC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
PubMed: 38922866
DOI: 10.1002/path.6318 -
Annals of Vascular Diseases Jun 2024Lymphedema is caused by dysfunction of the lymphatic system. It is divided into primary edema with no apparent cause and secondary edema with an exogenous cause. The... (Review)
Review
Lymphedema is caused by dysfunction of the lymphatic system. It is divided into primary edema with no apparent cause and secondary edema with an exogenous cause. The main symptoms are edema and heaviness, skin changes such as skin hardening, lymphocysts, lymphorrhoea, papillomas, and recurrent cellulitis. They are often irreversible and progressive, thus greatly reducing quality of life of the patients. Diagnosis is made by image examinations that can evaluate lymphatic flow and functions such as lymphoscintigraphy and indocyanine green fluorescence lymphangiography. Linear pattern and dermal backflow are the main findings. Conservative treatment consists of four components: compression therapy with elastic garments, exercise therapy, manual lymphatic drainage, and skin care, which is called complex physical therapy (CPT). Although CPT has become the gold standard of treatment, with evidence of efficacy reported in terms of volume reduction, maintenance, and prevention of cellulitis, it is a symptomatic treatment and does not improve impaired lymphatic flow. On the other hand, surgical treatment, such as lymphaticovenous anastomosis and vascularized lymph node transplantation, can create new lymphatic flow and improve lymphatic dysfunctions. Although these techniques are expected to be effective in volume reduction, cellulitis prevention, and improving quality of life, there is a need for more studies with a higher level of evidence in the future. In Japan, lymphedema is treated with a combination of conservative and surgical therapies, but lymphedema is intractable and few cases are completely cured. Therefore, how to improve the outcome of treatment is an important issue to be addressed in the future. (This is a translation of Jpn J Vasc Surg 2023; 32: 141-146.).
PubMed: 38919315
DOI: 10.3400/avd.ra.24-00011 -
Asian Pacific Journal of Cancer... Jun 2024
Review
Topics: Humans; India; Papillomavirus Vaccines; Health Knowledge, Attitudes, Practice; Papillomavirus Infections; Vaccination; Papillomaviridae; Uterine Cervical Neoplasms; Human Papillomavirus Viruses
PubMed: 38918643
DOI: 10.31557/APJCP.2024.25.6.1857 -
European Journal of Gastroenterology &... Jun 2024Lesbian, gay, bisexual, transgender, queer, or questioning individuals, as well as those with another diverse identity (LGBTQ+), present specific nuances in healthcare...
Lesbian, gay, bisexual, transgender, queer, or questioning individuals, as well as those with another diverse identity (LGBTQ+), present specific nuances in healthcare that physicians must consider in clinical practice. Particularly, gastroenterologists are nowadays facing different issues in several fields regarding LGBTQ+ healthcare, such as endoscopy, inflammatory bowel disease, hepatology, and proctology. In this study, the authors provide a practice-oriented and up-to-date review reinforcing the importance of some of the most prevalent pathologies associated with sexuality that gastroenterologists may encounter in their clinical practice. In terms of endoscopy, authors describe the endoscopic findings related to human papillomavirus (HPV) infection: the esophageal squamous papilloma and cell carcinoma; also highlight the importance of retroflexion maneuver during a routine colonoscopy that allows detection of anal intraepithelial neoplasia lesions that can be anal cancer precursors. Regarding inflammatory bowel disease, some considerations are made about the differential diagnosis with infectious proctitis, and the topic of the risk of anal cancer due to HPV infection, in this specific population, is also addressed. Considering hepatology, the authors review the most important issues related to hepatotropic sexually transmitted infections. The authors also make some comments regarding the possibility of drug-induced liver injury in gender-affirming hormone therapy and pre-exposure prophylaxis for HIV prevention. Finally, considering the proctology field, an up-to-date review is performed regarding anal cancer screening, HPV infection and related diseases, and infectious proctitis management.
PubMed: 38916210
DOI: 10.1097/MEG.0000000000002808 -
Journal of Controlled Release :... Jun 2024The development of high-purity antigens promotes the urgent need of novel adjuvant with the capability to trigger high levels of immune response....
The development of high-purity antigens promotes the urgent need of novel adjuvant with the capability to trigger high levels of immune response. Polyinosinic-polycytidylic (Poly(I:C)) is a synthetic double-stranded RNA (dsRNA) that can engage Toll-like receptor 3 (TLR3) to initiate immune responses. However, the Poly(I:C)-induced toxicity and inefficient delivery prevent its applications. In our study, combination adjuvants are formulated by aluminum oxyhydroxide nanorods (AlOOH NRs) and Poly(I:C), named Al-Poly(I:C), and the covalent interaction between the two components is further demonstrated. Al-Poly(I:C) mediates enhanced humoral and cellular immune responses in three antigen models, i.e., HBsAg virus-like particles (VLPs), human papilloma virus (HPV) VLPs and varicella-zoster virus (VZV) glycoprotein E (gE). Further mechanistic studies demonstrate that the dose and molecular weight (MW) of Poly(I:C) determine the physicochemical properties and adjuvanticity of the Al-Poly(I:C) combination adjuvants. Al-Poly(I:C) with higher Poly(I:C) dose promotes antigen-bearing dendritic cells (DCs) recruitment and B cells proliferation in lymph nodes. Al-Poly(I:C) formulated with higher MW Poly(I:C) induces higher activation of helper T cells, B cells, and CTLs. This study demonstrates that Al-Poly(I:C) potentiates the humoral and cellular responses in vaccine formulations. It offers insights for adjuvant design to meet the formulation requirements in both prophylactic and therapeutic vaccines.
PubMed: 38914205
DOI: 10.1016/j.jconrel.2024.06.054 -
Future Microbiology Jun 2024The value of preventive medicine is superior to treatment with vaccinations occupying high priority. Nevertheless, heavy pressure has started to form in regard to... (Review)
Review
The value of preventive medicine is superior to treatment with vaccinations occupying high priority. Nevertheless, heavy pressure has started to form in regard to strains not included in vaccines contributing to the changing epidemiology of pathogen subtypes leading to 'vaccine-induced strain replacement'. Among other mechanisms, increasing fitness of nonvaccine strains and metabolic shifts in the subtypes have been described. Classical examples include pneumococcal infections and viral diseases, such as the human papilloma virus. Recently, it has been described in SARS-CoV-2, leading to the emergence of new subtypes, such as Omicron and Delta variants. The phenomenon has also been reported in , and rotavirus. This study addresses the concepts, examples and implications of this phenomenon.
PubMed: 38913745
DOI: 10.1080/17460913.2024.2345003 -
Orbit (Amsterdam, Netherlands) Jun 2024Primary tumors of the lacrimal sac (PTLS) are a rare subtype of ocular adnexa tumors, with potentially life-threatening clinical course. There has been growing evidence...
Primary tumors of the lacrimal sac (PTLS) are a rare subtype of ocular adnexa tumors, with potentially life-threatening clinical course. There has been growing evidence of human papilloma virus (HPV) as an etiological agent in these tumors.In this retrospective observational case series, we report three cases of PTLS. All three underwent an initial dacryocystorhinostomy revealing a tissular mass in the lacrimal sac. Histological findings were respectively epithelial papilloma, epithelial Malpighian papilloma, and undifferentiated epidermoid carcinoma. PCR evaluation identified HPV serotype 6 in the first case and 16 in the third, and high p16 expression was found in the second case.These three cases of PTLS with HPV detection complement 36 other cases identified in the literature, further incriminating HPV in the pathogenesis of these neoplasms. Ophthalmologists must remain wary of chronic lacrimal occlusion symptoms, and resort to CT scan and orbital Doppler sonography whenever first-line treatment fails.
PubMed: 38913546
DOI: 10.1080/01676830.2024.2370056