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Understanding the role of nerves in head and neck cancers - a review.

Worldwide, head and neck cancers (HNCs) account for approximately 900,000 cases and 500,000 deaths annually, with their incidence continuing to rise. Carcinogenesis is a complex, multidimensional molecular process leading to cancer development, and in recent years, the role of nerves in the pathogenesis of various malignancies has been increasingly recognized. Thanks to the abundant innervation of the head and neck region, peripheral nervous system has gained considerable interest for its possible role in the development and progression of HNCs. Intratumoral parasympathetic, sympathetic, and sensory nerve fibers are emerging as key players and potential targets for novel anti-cancer and pain-relieving medications in different tumors, including HNCs. This review explores nerve-cancer interactions, including perineural invasion (PNI), cancer-related axonogenesis, neurogenesis, and nerve reprogramming, with an emphasis on their molecular mechanisms, mediators and clinical implications. PNI, an adverse histopathologic feature, has been widely investigated in HNCs. However, its prognostic value remains debated due to inconsistent results when classified dichotomously (present/absent). Emerging evidence suggests that quantitative and qualitative descriptions of PNI may better reflect its clinical usefulness. The review also examines therapies targeting nerve-cancer crosstalk and highlights the influence of HPV status on tumor innervation. By synthesizing current knowledge, challenges, and future perspectives, this review offers insights into the molecular basis of nerve involvement in HNCs and the potential for novel therapeutic approaches.

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Open Access Just Published
Understanding the role of nerves in head and neck cancers - a review

Worldwide, head and neck cancers (HNCs) account for approximately 900,000 cases and 500,000 deaths annually, with their incidence continuing to rise. Carcinogenesis is a complex, multidimensional molecular process leading to cancer development, and in recent years, the role of nerves in the pathogenesis of various malignancies has been increasingly recognized. Thanks to the abundant innervation of the head and neck region, peripheral nervous system has gained considerable interest for its possible role in the development and progression of HNCs. Intratumoral parasympathetic, sympathetic, and sensory nerve fibers are emerging as key players and potential targets for novel anti-cancer and pain-relieving medications in different tumors, including HNCs. This review explores nerve-cancer interactions, including perineural invasion (PNI), cancer-related axonogenesis, neurogenesis, and nerve reprogramming, with an emphasis on their molecular mechanisms, mediators and clinical implications. PNI, an adverse histopathologic feature, has been widely investigated in HNCs. However, its prognostic value remains debated due to inconsistent results when classified dichotomously (present/absent). Emerging evidence suggests that quantitative and qualitative descriptions of PNI may better reflect its clinical usefulness. The review also examines therapies targeting nerve-cancer crosstalk and highlights the influence of HPV status on tumor innervation. By synthesizing current knowledge, challenges, and future perspectives, this review offers insights into the molecular basis of nerve involvement in HNCs and the potential for novel therapeutic approaches.

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Open Access Just Published
Status analysis of quality control of administered infusion solution with cytotoxic drugs.

The administered infusion solution is a sterile preparation that can be used directly for intravenous infusion in patients by mixing one or more intravenous drugs using aseptic operation technology. The pharmacy intravenous admixture service (PIVAS) center is a professional technical service department in hospitals, where the majority of inpatient-administered infusion solutions are prepared. During the processes of dissolution, dilution, preparation, storage, and use of intravenous drugs, the quality control of the administered infusion solution can be affected by various factors. At present, there are no relevant standards or guidance documents for the quality control of administered infusion solutions. Cytotoxic drugs are still the main treatment option for cancer patients and are mainly prepared in PIVAS centers in most hospitals. In this study, we mainly focused on the quality control of cytotoxic drug-administered infusion solutions and explored associated factors (diluent, container, concentration, temperature, and light), physical stability (visual appearance, pH, osmolality, and particulate matter), chemical stability (content), and biological stability (sterility). Most of the studies reviewed in this paper have insufficient data on the related factors and physicochemical stability of the administered infusion solutions. Research on the sterility of administered infusion solutions is particularly limited, with only one article addressing this aspect. Ensuring the quality of cytotoxic drug-administered infusion solutions is vital for the safe administration of drugs to cancer patients, so it is very important to enhance associated research. This article summarized the relevant literature on the quality control of cytotoxic drug-administered infusion solutions and provided a reference for safer and more efficient use of these drugs in clinical practice.

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Open Access
Biomarker testing in lung cancer: from bench to bedside.

Non-small-cell lung cancer (NSCLC) is the poster child of personalized medicine. With increased knowledge about biomarkers and the consequent improvement in survival rates, NSCLC has changed from being a therapeutic nihilistic disease to that characterized by therapeutic enthusiasm. The routine biomarkers tested in NSCLC are EGFR, ALK, and ROS1. However, several additional biomarkers have been added to the diagnostic landscape. Current guidelines recommend testing at least seven biomarkers upfront at the time of NSCLC diagnosis-emphasizing the wide range of targets and corresponding therapies that can be leveraged for disease management. Sequential single-gene testing is not only time-consuming but also leads to tissue exhaustion. Multigene panel testing using next-generation sequencing (NGS) offers an attractive diagnostic substitute that aligns with the evolving dynamics of precision medicine. NGS enables the identification of point mutations, insertions, deletions, copy number alterations, fusion genes, and microsatellite instability information needed to guide the potential use of targeted therapy. This article reviews the existing guidelines, proposed recommendations for NGS in non-squamous NSCLC, real-world data on its use, and the advantages of adopting broader panel-based NGS testing over single-gene testing.

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Open Access
RAGE and its ligands in breast cancer progression and metastasis.

Breast cancer is the most common form of cancer diagnosed worldwide and the leading cause of death in women globally, according to Globocan 2020. Hence, investigating novel pathways implicated in cancer progression and metastasis could lead to the development of targeted therapies and new treatment strategies in breast cancer. Recent studies reported an interplay between the receptor for advanced glycation end products (RAGE) and its ligands, S100 protein group, advanced glycation end products (AGEs) and high-mobility group box 1 protein (HMGB1) and breast cancer growth and metastasis. We used articles available in the NCBI website database PubMed to write this scoping review. The search words used were 'RAGE receptor' AND/OR 'breast cancer, RAGE ligands, glycation end products'. A total of 90 articles were included. We conducted a meta-analysis to assess the relationship between the RAGE rs1800624 polymorphism and breast cancer risk using fixed-effect or random-effect models to calculate odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). RAGE upon activation by its ligands enhances downstream signaling pathways, contributing to breast cancer cells migration, growth, angiogenesis, metastasis, and drug resistance. In addition, studies have shown that RAGE and its ligands influence the way breast cancer cells interact with immune cells present in the tumor microenvironment (macrophages, fibroblasts), thus regulating it to promote tumor growth and metastasis. Breast cancers with a high expression of RAGE are associated with poor prognosis. Targeting RAGE and its ligands impairs cell invasion and metastasis, showing promising potential for further research as potential prognostic biomarkers or targeted onco-therapeutics.

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Open Access
Lymphadenectomy in the treatment of sarcomas - indications and technique.

Sarcomas are a rare type of malignancy with limited treatment options so far. This analysis aimed to describe the impact of lymphadenectomy on treating sarcoma patients. Sarcomas characterized by lymphatic spread are rare. For this reason, lymphadenectomy is not a procedure that is performed frequently. However, there are histological subtypes that spread more frequently through lymphatic vessels, such as rhabdomyosarcoma (RMS), epithelioid sarcoma (ES), clear cell sarcoma (CCS), and angiosarcoma. On the other hand, synovial sarcoma (SS) is not characterized by an increased tendency to lymphogenous metastases. In our study, we focus on these subtypes of sarcomas. The relationship between lymphadenectomy results and the subsequent prognosis of the patients was investigated. Metastases in the lymph nodes are diagnosed synchronously with distant metastases or when the primary tumor is detected. At the same time, despite lymphadenectomy, sarcoma patients developed further distant metastases. Currently, lymphadenectomy is not a routinely recommended method of treatment for patients with sarcomas. Most often, its potential use is indicated in the case of epithelioid sarcoma, clear cell sarcoma, and rhabdomyosarcoma after a previous positive sentinel lymph node biopsy (SLNB) result. Multicenter randomized prospective clinical trials on the role of lymphadenectomy in the treatment of sarcomas are needed.

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Open Access
Investigation of the prevalence of latent tuberculosis in cancer patients compared to non-cancer patients: a case-control study.

Latent tuberculosis (TB) can reactivate in immunocompromised individuals, such as cancer patients undergoing chemotherapy, leading to severe complications. Understanding the prevalence of latent TB in this high-risk group is crucial, especially in regions with moderate to high TB burdens. This study aims to determine the prevalence of latent tuberculosis in cancer patients before chemotherapy and immunotherapy to guide preventive interventions and reduce the risk of TB reactivation. This case-control study was conducted at Sina Hospital in Tehran, Iran, from 2012 to 2022. A total of 392, including 107 newly diagnosed cancer (case) and 285 non-cancer (control) patients, were enrolled in this study. All patients had received the Bacillus Calmette-Guérin (BCG) vaccine at the age of one. They underwent a thorough clinical examination and were screened using the tuberculin skin test (TST) to detect latent TB. Any active TB cases were identified through acid-fast smear tests. The data collected from the study participants was then analyzed. The results showed no significant difference in the size of TST between cancer and non-cancer patients (cases: median = 2mm, IQR: 1-12; controls: median = 2mm, IQR: 1-5; p = 0.09). The prevalence of latent TB was 27.1% in cancer patients and 20.7% in non-cancer patients, with no significant association identified between latent TB and malignancies (P-value = 0.176). Over a median follow-up of 4years, mortality was significantly higher in cancer patients compared to controls (42.1% vs 1.8%; P< 0.001, OR = 40.64). Additionally, deceased patients exhibited a greater prevalence of latent TB (44% vs 19.3% in survivors; P< 0.001, OR = 3.28), and increased size of TST was associated with higher mortality risk among cancer patients. In conclusion, this study emphasizes the need for vigilant latent TB screening in cancer patients, given the association between larger TST sizes and increased mortality risk. While no direct link between cancer type and latent TB was found, proactive TB management remains crucial, particularly for those undergoing immunosuppressive therapy.

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Open Access
Prognostic and clinicopathological significance of survivin in gynecological cancer.

Survivin belongs to the inhibitor of apoptosis protein (IAP) family and is encoded by the baculoviral inhibitor of apoptosis repeat-containing, or BIRC5, gene. It is preferentially expressed in cancers with functional complexity in cell signaling cascades such as extracellular signal-regulated kinases (ERK), mitogen-activated protein kinases (MAPK), heat shock protein-90 (HSP90), epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription (STAT), hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), and others. Survivin plays a role in cell division and cell death, properties that have attracted a large body of research to decipher its therapeutic and prognostic significance in cancer. Survivin has tumor-promoting effects in endometrial (EC) and ovarian (OC) cancers, and its upregulation in endometrial cancer has been associated with poor overall survival (OS). While survivin protein is abundantly expressed in OC, it is barely detectable in normal ovarian tissue or benign ovarian tumors. Survivin expression is also a marker for cervical intraepithelial neoplasia (CIN) and high-risk human papillomavirus, and a predictor of viral clearance and prognosis in uterine cervical cancer (UCC). Furthermore, nuclear survivin expression is very low in normal vulvar squamous epithelium and increases to become abundant in vulvar invasive squamous cell carcinoma (ISCC), conferring resistance to apoptosis in vulvar carcinogenesis. In this review, we discuss in detail the impact of survivin signaling on gynecological cancers and provide insight on its therapeutic and diagnostic potential, existing research gaps, and areas for future research.

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Open Access
Evaluation of outcomes of psychological interventions in terminally ill family caregivers: a brief overview.

Family caregivers play a crucial role in supporting patients with incurable diseases, but often experience significant stress and anxiety. This study aimed to investigate the impact of psychological interventions on family caregivers, with a focus on reducing the burden of care, improving mental health and quality of life, and promoting family communication. This study conducted a brief overview of quantitative and qualitative research on assessing the impact of psychological interventions on family caregivers. A comprehensive literature search was conducted in PUBMED, SCOPUS, EMBASE, SCIENCE DIRECT and WEB OF SCIENCE to identify relevant papers, resulting in 20 articles being included. The included studies focused on evaluating the outcomes of psychological interventions on family caregivers. Ultimately, 20 relevant articles were retrieved from a pool of 500 articles, focusing on the evaluation of the primary outcomes of psychological interventions on family caregivers. The review of 20 articles revealed that interventions such as expressive writing and reminiscence therapy had a positive and significant impact on reducing the burden of care and fostering a positive care environment. Additionally, these interventions were found to be effective in improving self-esteem, family communication, and overall wellbeing. The study emphasizes the need for further research to confirm the benefits of these interventions and their role in promoting family resilience. These findings highlight the potential of psychological interventions in alleviating the challenges faced by family caregivers of patients with incurable diseases.

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Open Access